Abstract 13507: The Role of Weight Loss in Mediating the Effects of a 2-year Caloric Restriction Regimen on Cardiometabolic Risk Markers in Individuals Without Obesity

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
James L Dorling ◽  
Leanne Redman ◽  
Eric Ravussin ◽  
Kim Huffman ◽  
Susan B RACETTE ◽  
...  
Keyword(s):  
Weight Loss ◽  
Caloric Restriction ◽  
Cardiometabolic Risk ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Model Assessment ◽  
Risk Markers ◽  
Mediation Analyses ◽  
Cardiometabolic Risk Markers ◽  
The Impact

Introduction: Caloric restriction (CR) improves cardiometabolic risk, even among individuals without obesity. However, it is unclear whether these aging-related benefits are mediated by weight loss. Mediation analyses inform mechanisms underlying relationships between an exposure and outcome. Using mediation analyses, our aim was to test if 2-year weight loss mediates the beneficial effects of CR on cardiometabolic risk markers in individuals without obesity. Methods: Participants without obesity were randomized 2:1 to CR or ad libitum (AL) as part of the 2-year trial, Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). The CR group aimed to enact 25% CR for 2 years, while AL maintained habitual energy intake. Baseline and year 2 assessments included weight and cardiometabolic risk markers. Using the approaches of Valeri and VanderWeele, mediation was quantified as the natural indirect effect (NIE), defined as the impact of an exposure on an outcome through a mediator. Here, the NIE was the effect of CR (exposure) on cardiometabolic risk markers (outcome) that was accounted for by weight change (mediator). Results: In total, 117 and 71 participants in the CR and AL groups, respectively, completed the trial. The CR group achieved 11.9 (± 0.7)% CR and 7.6 (± 0.3) kg of weight loss ( P < 0.01 versus AL). Weight loss significantly mediated the CR-induced improvements in total cholesterol (NIE = -10.4 ± 3.5 mg/dL), low-density lipoprotein cholesterol (NIE = -8.5 ± 2.8 mg/dL), high-density lipoprotein cholesterol (NIE = 2.9 ± 1.3 mg/dL), triglycerides (NIE = -0.20 ± 0.05 log mg/dL), the homeostatic model assessment of insulin resistance (NIE = -0.22 ± 0.06), and C-reactive protein (NIE = -0.39 ± 0.15 log ug/mL) ( P ≤ 0.02). Weight loss did not mediate CR-induced reductions in systolic (NIE = -0.9 ± 1.4 mmHg) and diastolic (NIE = -1.0 ± 1.1 mmHg) blood pressure ( P ≥ 0.37). Conclusion: In individuals without obesity, CR-induced improvements in multiple cardiometabolic risk markers are driven by weight loss after 2 years. These findings emphasize that, even in individuals without obesity, weight loss after prolonged CR plays a role in improving cardiometabolic disease risk; however, some CR benefits still occur independent of weight loss.

scholarly journals Impact of the Apolipoprotein E (epsilon) Genotype on Cardiometabolic Risk Markers and Responsiveness to Acute and Chronic Dietary Fat Manipulation

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2044 ◽  
Author(s):  
Kumari M. Rathnayake ◽  
Michelle Weech ◽  
Kim G. Jackson ◽  
Julie A. Lovegrove
Keyword(s):  
Dietary Fat ◽  
Cardiometabolic Risk ◽  
Apoe Genotype ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Risk Markers ◽  
Cardiometabolic Risk Markers ◽  
The Impact ◽  
Volume Pulse ◽  
Digital Volume Pulse

Apolipoprotein (APO) E (ε) genotype is considered to play an important role in lipid responses to dietary fat manipulation but the impact on novel cardiometabolic risk markers is unclear. To address this knowledge gap, we investigated the relationship between the APOE genotype and cardiometabolic risk markers in response to acute and chronic dietary fat intakes. Associations with fasting (baseline) outcome measures (n = 218) were determined using data from the chronic DIVAS (n = 191/195 adults at moderate cardiovascular disease risk) and acute DIVAS-2 (n = 27/32 postmenopausal women) studies examining the effects of diets/meals varying in saturated, polyunsaturated and monounsaturated (MUFA) fatty acid composition. Participants were retrospectively genotyped for APOE (rs429358, rs7412). For baseline cardiometabolic outcomes, E4 carriers had higher fasting total and low-density lipoprotein-cholesterol (LDL-C), total cholesterol: high-density lipoprotein-cholesterol (HDL-C) and LDL-C: HDL-C ratios, but lower C-reactive protein (CRP) than E3/E3 and E2 carriers (p ≤ 0.003). Digital volume pulse stiffness index was higher in E2 carriers than the E3/E3 group (p = 0.011). Following chronic dietary fat intake, the significant diet × genotype interaction was found for fasting triacylglycerol (p = 0.010), with indication of a differential responsiveness to MUFA intake between the E3/E3 and E4 carriers (p = 0.006). Test fat × genotype interactions were observed for the incremental area under the curve for the postprandial apolipoprotein B (apoB; p = 0.022) and digital volume pulse reflection index (DVP-RI; p = 0.030) responses after the MUFA-rich meals, with a reduction in E4 carriers and increase in the E3/E3 group for the apoB response, but an increase in E4 carriers and decrease in the E3/E3 group for the DVP-RI response. In conclusion, baseline associations between the APOE genotype and fasting lipids and CRP confirm previous findings, although a novel interaction with digital volume pulse arterial stiffness was observed in the fasted state and differential postprandial apoB and DVP-RI responses after the MUFA-rich meals. The reported differential impact of the APOE genotype on cardiometabolic markers in the acute and chronic state requires confirmation.

scholarly journals Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome

2021 ◽  
Author(s):  
L. Montefusco ◽  
F. D’Addio ◽  
C. Loretelli ◽  
M. Ben Nasr ◽  
M. Garziano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Weight Loss ◽  
Caloric Restriction ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Model Assessment ◽  
Adult Males ◽  
Positive Effects ◽  
Cytokine Profiles

Abstract Background Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. Aim To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. Methods Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. Results After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1β, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. Conclusion Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk. Graphic abstract

scholarly journals The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans—A Systematic Review and Meta-Analysis

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 991 ◽  
Author(s):  
Eva Fechner ◽  
Ellen T.H.C. Smeets ◽  
Patrick Schrauwen ◽  
Ronald P. Mensink
Keyword(s):  
Total Cholesterol ◽  
Cardiometabolic Risk ◽  
Meta Analysis ◽  
Saturated Fatty Acids ◽  
Low Density Lipoprotein ◽  
Random Effect ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Risk Markers ◽  
Cardiometabolic Risk Markers

Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1) moderate-low CHO diets (<45–40 E%, n = 13), (2) low CHO diets (<40–30 E%, n = 16), and (3) very-low CHO diets (<30–3 E%; n = 8). Summary estimates of weighted mean differences (WMDs) in selected risk markers were calculated using random-effect meta-analyses. Differences between the LCD groups were assessed with univariate meta-regression analyses. Overall, the LCDs resulted in significant weight loss, reduced diastolic blood pressure BP, and increased total cholesterol and high-density lipoprotein cholesterol (HDL-C), without significant differences between the three LCD groups. Higher low-density lipoprotein cholesterol (LDL-C) concentrations were found with the very-low CHO diets compared to the moderate-low CHO diets. Decreases in triacylglycerol (TAG) concentrations were more pronounced with the low and very-low CHO diets, compared to the moderate-low CHO diets. Substitution of CHO by mainly saturated fatty acids (SFAs) increased total cholesterol, LDL-C, and HDL-C concentrations. Except for LDL-C and TAGs, effects were not related to the degree of CHO restriction. Potential effects of nutrient exchanges should be considered when following LCDs.

scholarly journals Baseline cardiometabolic profiles and SARS-CoV-2 infection in the UK Biobank

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248602 ◽  
Author(s):  
Ryan J. Scalsky ◽  
Yi-Ju Chen ◽  
Karan Desai ◽  
Jeffery R. O’Connell ◽  
James A. Perry ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type Ii Diabetes ◽  
Cardiometabolic Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Type Ii ◽  
Uk Biobank ◽  
The Uk ◽  
The Impact

Background SARS-CoV-2 is a rapidly spreading coronavirus responsible for the Covid-19 pandemic, which is characterized by severe respiratory infection. Many factors have been identified as risk factors for SARS-CoV-2, with much early attention being paid to body mass index (BMI), which is a well-known cardiometabolic risk factor. Objective This study seeks to examine the impact of additional baseline cardiometabolic risk factors including high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB), triglycerides, hemoglobin A1c (HbA1c) and diabetes on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. Methods We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. Results Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL-C and ApoA-I were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL-C was controlled, the effect of HDL-C remained significant when BMI was controlled for. LDL-C, ApoB and triglyceride levels were not found to be significantly associated with increased odds. Conclusion Elevated HDL-C and ApoA-I levels were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL-C, suggesting that these effects may be mediated in part through regulation of HDL-C levels. In summary, our study suggests that baseline HDL-C level may be useful for stratifying SARS-CoV-2 infection risk and corroborates the emerging picture that HDL-C may confer protection against sepsis in general and SARS-CoV-2 in particular.

scholarly journals Cardiometabolic risk markers of normal weight and excess body weight in Brazilian adolescents

2016 ◽  
Vol 41 (6) ◽  
pp. 659-665 ◽  
Author(s):  
Silmara Salete de Barros Silva Mastroeni ◽  
Marco Fabio Mastroeni ◽  
Muryel de Carvalho Gonçalves ◽  
Guilherme Debortoli ◽  
Nilza Nunes da Silva ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Normal Weight ◽  
Lipoprotein Cholesterol ◽  
Socioeconomic Background ◽  
Excess Body Weight ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Risk Markers

Excess body weight leads to a variety of metabolic changes and increases the risk for cardiovascular diseases (CVD) in adulthood. The objective of this study was to investigate the presence of risk markers for CVD among Brazilian adolescents of normal weight and with excess body weight. The markers included blood pressure, C-reactive protein, homocysteine, tumor necrosis factor alpha, fibrinogen, fasting insulin and glucose, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides. We calculated odds ratios (OR) using logistic regression and adjusted for potential confounders such as age, sex, physical activity, and socioeconomic background. Compared with normal weight subjects, overweight/obese adolescents were more likely to have higher systolic blood pressure (OR = 3.49, p < 0.001), fasting insulin (OR = 8.03, p < 0.001), HOMA-IR (OR = 8.03, p < 0.001), leptin (OR = 5.55, p < 0.001), and LDL-c (OR = 5.50, p < 0.001) and lower serum HDL-c concentrations (OR = 2.76, p = 0.004). After adjustment for confounders, the estimates did not change substantially, except for leptin for which the risk associated with overweight increased to 11.09 (95% CI: 4.05–30.35). In conclusion, excess body weight in adolescents exhibits strong associations with several markers that are established as causes of CVD in adults. This observation stresses the importance of primary prevention and of maintaining a healthy body weight throughout adolescence to reduce the global burden of CVD.

scholarly journals Diet-Induced Weight Loss Reduces DNA Damage and Cardiometabolic Risk Factors in Overweight/Obese Women with Polycystic Ovary Syndrome

2016 ◽  
Vol 68 (3) ◽  
pp. 220-227 ◽  
Author(s):  
Nayara Pereira Soares ◽  
Ana Celly Souza dos Santos ◽  
Eduardo Caldas Costa ◽  
George Dantas Azevedo ◽  
Débora Cristina Damasceno ◽  
...  
Keyword(s):  
Risk Factors ◽  
Dna Damage ◽  
Weight Loss ◽  
Polycystic Ovary Syndrome ◽  
Cardiometabolic Risk ◽  
Polycystic Ovary ◽  
Cardiometabolic Risk Factors ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
The Impact

Aims: We aimed to investigate the impact of following a diet to induce weight loss (500 kcal deficit per day) over DNA damage and cardiometabolic risk factors in women with overweight/obesity diagnosed with polycystic ovary syndrome (PCOS). Methods: A study was conducted in Natal, RN, Brazil selecting overweight/obese (body mass index ≥25 and <39 kg/m2) women (18-35 years). The levels of DNA damage were assessed by a single cell gel electrophoresis. Repeated 24 h dietary recall questionnaires, anthropometry, biochemical profile and sex hormones were collected at baseline and after 12 weeks of intervention. Results: Women exhibiting a decrease in the markers of DNA damage: tail intensity (24.35 ± 5.86 - pre diet vs. 17.15 ± 5.04 - post-diet; p < 0.001) and tail moment (20.47 ± 7.85 - pre diet vs. 14.13 ± 6.29 - post-diet; p < 0.002). Reduction of calorie intake, weight loss, decreased sexual hormone and cardiometabolic markers such as insulin, homeostasis model assessment of insulin resistance and low-density lipoprotein cholesterol were verified In the multivariate regression analysis, quantitative insulin sensitivity check index and progesterone were responsible for the variation markers in DNA damage before the diet, losing its influence upon diet. Conclusion: DNA damage and the impact of cardiometabolic risk factors decreased after the intervention in women with PCOS, indicating the relevance of a nutritional approach in this group of patients.

scholarly journals Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness—the LIFE-Adult Study

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Franziska G. Rauscher ◽  
Mengyu Wang ◽  
Mike Francke ◽  
Kerstin Wirkner ◽  
Anke Tönjes ◽  
...  
Keyword(s):  
Renal Function ◽  
Cardiometabolic Risk ◽  
Density Lipoprotein ◽  
Population Based ◽  
Risk Markers ◽  
Regression Analyses ◽  
Fiber Layer ◽  
Nerve Fiber Layer Thickness ◽  
Cardiometabolic Risk Markers ◽  
Sd Oct

Abstract Background Circumpapillary retinal nerve fiber layer thickness (cpRNFLT) as assessed by spectral domain optical coherence tomography (SD-OCT) is a new technique used for the detection and evaluation of glaucoma and other optic neuropathies. Before translating cpRNFLT into clinics, it is crucially important to investigate anthropometric, biochemical, and clinical parameters potentially affecting cpRNFLT in a large population-based dataset. Methods The population-based LIFE-Adult Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. All participants underwent standardized systemic assessment of various cardiometabolic risk markers and ocular imaging, including cpRNFLT measurement using SD-OCT (Spectralis, Heidelberg Engineering). After employing strict SD-OCT quality criteria, 8952 individuals were analyzed. Multivariable linear regression analyses were used to evaluate the independent associations of various cardiometabolic risk markers with sector-specific cpRNFLT. For significant markers, the relative strength of the observed associations was compared to each other to identify the most relevant factors influencing cpRNFLT. In all analyses, the false discovery rate method for multiple comparisons was applied. Results In the entire cohort, female subjects had significantly thicker global and also sectoral cpRNFLT compared to male subjects (p < 0.05). Multivariable linear regression analyses revealed a significant and independent association between global and sectoral cpRNFLT with biomarkers of renal function and lipid profile. Thus, thinner cpRNFLT was associated with worse renal function as assessed by cystatin C and estimated glomerular filtration rate. Furthermore, an adverse lipid profile (i.e., low high-density lipoprotein (HDL) cholesterol, as well as high total, high non-HDL, high low-density lipoprotein cholesterol, and high apolipoprotein B) was independently and statistically significantly related to thicker cpRNFLT. In contrast, we do not observe a significant association between cpRNFLT and markers of inflammation, glucose homeostasis, liver function, blood pressure, or obesity in our sector-specific analysis and globally. Conclusions Markers of renal function and lipid metabolism are predictors of sectoral cpRNFLT in a large and deeply phenotyped population-based study independently of previously established covariates. Future studies on cpRNFLT should include these biomarkers and need to investigate whether incorporation will improve the diagnosis of early eye diseases based on cpRNFLT.

scholarly journals The effect of a low carbohydrate high fat diet on emerging biochemical markers of cardiometabolic risk

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Deaglan McCullough ◽  
Tanja Harrison ◽  
Katie Lane ◽  
Lynne Boddy ◽  
Farzad Amirabdollahian ◽  
...  
Keyword(s):  
Cardiometabolic Risk ◽  
Metabolic Adaptation ◽  
Model Assessment ◽  
High Fat ◽  
Low Carbohydrate ◽  
Homeostatic Model Assessment ◽  
Ad Libitum ◽  
Cardiometabolic Risk Markers ◽  
The Uk ◽  
The Impact

AbstractWorldwide, cardiovascular disease (CVD) is the number 1 cause of mortality and is associated with insulin resistance (IR). Emerging biomarkers such as FGF21 and adiponectin are associated with cardiometabolic risk. Low carbohydrate, high fat (LCHF) diets have been reported to reduce cardiometabolic risk markers; however, few studies have compared a LCHF diet vs. a high carbohydrate (HC), lower fat diet under ad libitum conditions on adiponectin and FGF21. The purpose of this study was to investigate the effects of an ad libitum LCHF vs. HC diet on IR, FGF21 and adiponectin in 16 healthy adults. Ethical approval: Liverpool John Moores University Research Ethics Committee (16/ELS/029); registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly assigned to a HC diet (n = 8, the UK Eatwell guidelines; ≥ 50% of energy from carbohydrates) or a LCHF diet (n = 8, consume < 50 g/day of carbohydrates). All provided plasma samples at 0, 4 and 8 weeks. FGF21 (R&D Systems) was analysed via ELISA and adiponectin, insulin and glucose were analysed via immunoassay technology (Randox Evidence Investigator™ Metabolic Syndrome Arrays I & II). Mann Whitney, Friedmans, Wilcoxon tests and 2×3 ANOVA (IBM SPSS 25®) were undertaken to investigate significant differences between and within groups. The homeostatic model assessment (HOMA) was used to calculate IR. FGF21 significantly (P = 0.04) decreased (Mdn, IQR:148.16, 78.51–282.02 to 99.4, 39.87–132.29 pg/ml) after 4 weeks and significantly (P = 0.02) increased (Mdn, IQR:167.38, 80.82–232.89 pg/ml) by 8 weeks vs. baseline with LCHF. No significant differences (P > 0.05) were observed between groups. Adiponectin was significantly (P = 0.03) different at week 4 only between groups. Adiponectin increased after 4 weeks (Mdn, IQR:13.44, 9.12–25.47 to 16.64, 11.96–21.51 ng/ml) but was only significantly (P = 0.03) different by 8 weeks vs. baseline in the HC group (Mdn, IQR:16, 10.8–27.43 ng/ml). Adiponectin remained unchanged (P = 0.96) in the LCHF group. HOMA significantly decreased with both diets after 8 weeks only (mean ± SD, LCHF: 2.9 ± 1.3 to 1.8 ± 0.8, HC: 2.5 ± 0.6 to 1.9 ± 0.6, P = 0.008) but was not significantly (P = 0.60) different between groups. These preliminary data reveal that while both diets improved insulin sensitivity, they may do so by different mechanisms. Future studies are warranted to investigate further, how a LCHF vs. HC diet affects FGF21 and adiponectin, and the subsequent regulation of IR. Furthermore, studies that extend these findings by determining the impact of LCHF vs. HC on peripheral metabolism to determine potential nutrition-mediated mechanisms of metabolic adaptation are warranted.

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