Postpartum weight retention and the early evolution of cardiovascular risk over the first 5 years after pregnancy.

BACKGROUND: The cumulative effect of postpartum weight retention from each pregnancy in a woman's life may contribute to her risk of ultimately developing type 2 diabetes and cardiovascular disease. However, there is limited direct evidence supporting this hypothesis. Thus, we sought to characterize the impact of postpartum weight retention on the trajectories of cardiovascular risk factors over the first 5-years after pregnancy. METHODS: In this prospective observational cohort study, 330 women (mean age 35.7 ± 4.3 years, mean pre-pregnancy body mass index 25.2 ± 4.8 kg/m2, 50.9% primiparous) underwent serial cardiometabolic characterization (anthropometry, blood pressure, lipids, oral glucose tolerance test, insulin sensitivity/resistance (Matsuda index, HOMA-IR), C-reactive protein (CRP), adiponectin) at 1-year, 3-years, and 5-years postpartum. Based on the magnitude of weight change between pre-pregnancy and 5-years postpartum, they were stratified into the following 3 groups: weight loss (n = 100), weight gain 0-6% (n = 110), and weight gain ≥ 6% (n = 120). RESULTS: At 1-year postpartum, cardiovascular risk factors did not differ between the groups. However, an adverse risk factor profile progressively emerged in the weight retention groups at 3- and 5-years. Indeed, after covariate adjustment, there was stepwise worsening (from the weight loss group to weight gain 0-6% to weight gain ≥ 6% group) of the following cardiovascular risk factors at 5-years: triglycerides (p = 0.001), HDL (p = 0.02), LDL (p = 0.01), apolipoprotein-B (p = 0.003), Matsuda index (p < 0.0001), HOMA-IR (p < 0.0001), fasting glucose (p = 0.07), and CRP (p = 0.01). Moreover, on logistic regression analyses, weight gain ≥ 6% emerged as an independent predictor of pre-diabetes/diabetes at 5-years (adjusted OR = 3.40, 95%CI: 1.63-7.09). CONCLUSION: Postpartum weight retention predicts trajectories of worsening cardiovascular risk factors and glucose intolerance over the first 5-years after delivery, consistent with its postulated contribution to future vascular disease in women.

Future cardiometabolic implications of insulin hypersecretion in response to oral glucose: a prospective cohort study.

Background: The cardiometabolic implications of postprandial hyperinsulinemia are unclear with recent studies suggesting both adverse and beneficial associations. We aimed to evaluate the longitudinal cardiometabolic implications of the post-challenge insulin secretory response over 4-years follow-up. Methods: In this prospective cohort study, conducted in Toronto (Ontario, Canada), women comprising the full range of antepartum glucose tolerance were recruited in pregnancy (at the time of glucose tolerance screening, late in the second trimester) to undergo cardiometabolic testing in the years thereafter. Participants underwent oral glucose tolerance tests (OGTT) at 1-year, 3-years, and 5-years postpartum, enabling serial assessment of cardiovascular risk factors, glucose tolerance, insulin sensitivity or resistance (Matsuda index, HOMA-IR), and beta-cell function-via Insulin Secretion-Sensitivity Index-2 (ISSI-2) and insulinogenic index/HOMA-IR (IGI/HOMA-IR). Baseline post-challenge insulinemia was assessed with the corrected insulin response (CIR) at 1-year. Cardiometabolic factors were compared between baseline CIR tertiles. Findings: Between Oct 23, 2003 and March 31, 2014, 306 women were enrolled. In this study population, there was progressive worsening of waist circumference (p = 0.016), HDL (p = 0.018), CRP (p = 0.006), and insulin sensitivity (p < 0.001) from the lowest to middle to highest tertile of CIR at 1-year. However, these adverse features were accompanied by progressively better beta-cell function (both p < 0.001), coupled with lower fasting and 2-h glucose on the OGTT (both p < 0.001). On adjusted longitudinal analyses, higher CIR tertile at 1-year was independently associated with (i) higher ISSI-2 and IGI/HOMA-IR and (ii) lower fasting and 2-h glucose at both 3-years and 5-years (all p < 0.001), but was not associated with BMI, waist, lipids, CRP or insulin sensitivity/resistance. The highest CIR tertile at 1-year predicted lower risk of pre-diabetes or diabetes at both 3-years (adjusted OR = 0.19; 95% CI 0.08-0.45) and 5-years (aOR = 0.18; 0.08-0.39), relative to the lowest tertile. Interpretation: A robust post-challenge insulin secretory response does not indicate adverse cardiometabolic health but, rather, portends favourable metabolic function in the years to come. Future long-term study of the implications of the post-challenge insulinemic response is warranted. Funding: Canadian Institutes of Health Research.

Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes.

Context: Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined. Objective: Our objective was to assess the association of uVDBP with longitudinal changes in kidney function. Methods: Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates. Results: Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 µg/mmol, 2.63 µg/mmol, and 2.48 µg/mmol, respectively, and ACR positively correlated with uVDBP concentrations (r = 0.37; P < .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (ß = 30.67 and ß = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.

Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis.

Importance: Concerns have been raised that frequent consumption of 100% fruit juice may promote weight gain. Current evidence on fruit juice and weight gain has yielded mixed findings from both observational studies and clinical trials. Objective: To synthesize the available evidence on 100% fruit juice consumption and body weight in children and adults. Data Sources: MEDLINE, Embase, and Cochrane databases were searched through May 18, 2023. Study Selection: Prospective cohort studies of at least 6 months and randomized clinical trials (RCTs) of at least 2 weeks assessing the association of 100% fruit juice with body weight change in children and adults were included. In the trials, fruit juices were compared with noncaloric controls. Data Extraction and Synthesis: Data were pooled using random-effects models and presented as ß coefficients with 95% CIs for cohort studies and mean differences (MDs) with 95% CIs for RCTs. Main Outcomes and Measures: Change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was assessed in children and change in body weight in adults. Results: A total of 42 eligible studies were included in this analysis, including 17 among children (17 cohorts; 0 RCTs; 45 851 children; median [IQR] age, 8 [1-15] years) and 25 among adults (6 cohorts; 19 RCTs; 268 095 adults; median [IQR] age among cohort studies, 48 [41-61] years; median [IQR] age among RCTs, 42 [25-59]). Among cohort studies in children, each additional serving per day of 100% fruit juice was associated with a 0.03 (95% CI, 0.01-0.05) higher BMI change. Among cohort studies in adults, studies that did not adjust for energy showed greater body weight gain (0.21 kg; 95% CI, 0.15-0.27 kg) than studies that did adjust for energy intake (-0.08 kg; 95% CI, -0.11 to -0.05 kg; P for meta-regression <.001). RCTs in adults found no significant association of assignment to 100% fruit juice with body weight but the CI was wide (MD, -0.53 kg; 95% CI, -1.55 to 0.48 kg). Conclusion and Relevance: Based on the available evidence from prospective cohort studies, in this systematic review and meta-analysis, 1 serving per day of 100% fruit juice was associated with BMI gain among children. Findings in adults found a significant association among studies unadjusted for total energy, suggesting potential mediation by calories. Further trials of 100% fruit juice and body weight are desirable. Our findings support guidance to limit consumption of fruit juice to prevent intake of excess calories and weight gain.

Impact of the diagnosis of gestational diabetes on maternal physical activity after pregnancy.

AIM: The diagnosis of gestational diabetes (GDM) identifies women who are at future risk of developing type 2 diabetes. However, it is unclear if diagnosing GDM thus motivates women to increase physical activity after pregnancy or if this medicalization has the opposite effect of decreasing activity, possibly reflecting assumption of a sick role. We thus sought to evaluate the impact of diagnosing GDM on changes in maternal physical activity after pregnancy. METHODS: In this prospective cohort study, physical activity patterns were assessed by the Baecke questionnaire for the year before pregnancy and the first year postpartum in 405 white women comprising the following three gestational glucose tolerance groups: (a) those who did not have GDM (non-GDM; n = 247), (b) women with undiagnosed GDM (n = 46) and (c) those diagnosed with GDM (n = 112). RESULTS: In the year before pregnancy, mean adjusted total physical activity progressively decreased from non-GDM to undiagnosed GDM to diagnosed GDM (p = .067). Conversely, at 1 year postpartum, total physical activity was highest in those who had been diagnosed with GDM (p = .02). Compared with non-GDM, diagnosed GDM predicted an increase in total physical activity from pre-pregnancy to 1 year postpartum (t = 2.3, p = .02) whereas undiagnosed GDM predicted a concurrent decrease in leisure-time activity (t = -2.74, p = .006). Accordingly, the mean adjusted increase in body mass index from pre-pregnancy to 1 year postpartum was lowest in those with diagnosed GDM (0.26 ± 0.25 kg/m2 ), highest in undiagnosed GDM (1.23 ± 0.38 kg/m2 ) and intermediate in non-GDM (0.89 ± 0.22 kg/m2 ) (overall p = .04). CONCLUSION: Diagnosis of GDM leads to increased physical activity after pregnancy that may partially attenuate postpartum weight retention.

Determinants of Anishinabeck infant and early childhood growth trajectories in Northwestern Ontario, Canada: a cohort study.

BACKGROUND: The Developmental Origins of Health and Disease (DOHaD) paradigm emphasizes the significance of early life factors for the prevention of chronic health conditions, like type 2 diabetes (T2DM) and obesity, which disproportionately affect First Nations communities in Canada. Despite increasing DOHaD research related to maternal health during pregnancy, early childhood growth patterns, and infant feeding practices with many populations, data from First Nations communities in Canada are limited. In partnership with Sandy Lake First Nation, the aims of this project were to characterize birthweights and growth patterns of First Nations infants/children over the first 6 years of life and to study the impact of maternal and infant social and behavioral factors on birthweight and growth trajectories. METHODS: We recruited 194 families through community announcements and clinic visits. Infant/child length/height and weight were measured at 1 and 2 weeks; 1, 2, 6, 12, and 18 months; and 2, 3, 4, 5 and 6 years. Maternal and infant/child questionnaires captured data about health, nutrition, and social support. Weight-for-Age z-score (WAZ), Height-for-Age z-score (HAZ), and BMI-for-Age z-score (BAZ) were calculated using WHO reference standards and trajectories were analyzed using generalized additive models. Generalized estimating equations and logistic regression were used to determine associations between exposures and outcomes. RESULTS: WAZ and BAZ were above the WHO mean and increased with age until age 6 years. Generalized estimating equations indicated that WAZ was positively associated with age (0.152; 95% CI 0.014, 0.29), HAZ was positively associated with birthweight (0.155; 95% CI 0.035, 0.275), and BAZ was positively associated with caregiver's BMI (0.049; 95% CI 0.004, 0.090). There was an increased odds of rapid weight gain (RWG) with exposure to gestational diabetes (OR: 7.47, 95% CI 1.68, 46.22). Almost 70% of parents initiated breastfeeding, and breastfeeding initiation was modestly associated with lower WAZ (-0.18; 95% CI -0.64, 0.28) and BAZ (-0.23; 95% CI -0.79, 0.34). CONCLUSIONS: This work highlights early life factors that may contribute to T2DM etiology and can be used to support community and Indigenous-led prevention strategies.

Deteriorating beta cell function is the dominant determinant of progression from normal glucose tolerance to prediabetes/diabetes in young women following pregnancy.

AIMS/HYPOTHESIS: Excess adiposity, insulin resistance and beta cell dysfunction each contribute to the development of prediabetes (impaired glucose tolerance and/or impaired fasting glucose)/diabetes but their comparative impact in relation to one another remains uncertain. We thus ranked their contributions to incident dysglycaemia over the first 5 years postpartum in women reflecting the full spectrum of gestational glucose tolerance (spanning normoglycaemia to gestational diabetes) and hence a range of future diabetic risk. METHODS: In this study, 302 women with normal glucose tolerance (NGT) on OGTT at 3 months postpartum underwent repeat OGTT at 1 year, 3 years and 5 years, enabling serial assessment of glucose tolerance, insulin sensitivity/resistance (Matsuda index, HOMA-IR) and beta cell function (insulin secretion-sensitivity index-2 [ISSI-2], insulinogenic index [IGI]/HOMA-IR). Determinants of prediabetes/diabetes were ranked by change in concordance index (CCI) of Cox proportional hazard regression models. RESULTS: Over 5 years of follow-up, 89 women progressed from NGT to prediabetes/diabetes (progressors). At 3 months postpartum, though all women were normoglycaemic, future progressors had higher fasting glucose (p=0.03) and 2 h glucose (p<0.0001) than non-progressors, coupled with higher BMI (p=0.001), greater insulin resistance (both Matsuda index and HOMA-IR, p≤0.02) and poorer beta cell function (both ISSI-2 and IGI/HOMA-IR, p≤0.006). Unlike their peers, progressors exhibited deteriorating beta cell function from 1 year to 5 years (both p<0.0001). On regression analyses, the dominant determinants of progression to prediabetes/diabetes were time-varying ISSI-2 (change in CCI 25.2%) and IGI/HOMA-IR (13.0%), in contrast to time-varying Matsuda index (2.9%) and HOMA-IR (0.5%). Neither time-varying BMI nor waist were significant predictors after adjustment for beta cell function and insulin sensitivity/resistance. CONCLUSION/INTERPRETATION: Declining beta cell function is the dominant determinant of incident prediabetes/diabetes in young women following pregnancy.

Association of Serum Very-Long-Chain Saturated Fatty Acids With Changes in Insulin Sensitivity and ß-Cell Function: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort.

A unique group of circulating very-long-chain saturated fatty acids (VLCSFAs), including arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have been associated with a lower risk of type 2 diabetes, although associations with early metabolic risk phenotypes preceding type 2 diabetes have received limited study. We aimed to examine the associations of VLCSFAs with longitudinal changes in insulin sensitivity and ß-cell function in a cohort at risk for type 2 diabetes. VLCSFAs in the four main serum pools (phospholipid, triacylglycerol, cholesteryl ester, and nonesterified fatty acid) were extracted from fasting baseline samples (n = 467). Generalized estimating equations were used to determine the associations between VLCSFAs and changes over 9 years in validated indices of insulin sensitivity (HOMA2-%S [insulin sensitivity as percentage of normal population and ISI) and ß-cell function (insulinogenic index [IGI], IGI divided by HOMA-insulin resistance [IGI/IR], and insulin secretion sensitivity index 2 [ISSI-2]). Associations of VLCSFAs with outcomes were strongest in the triacylglycerol lipid pool: 20:0 was positively associated with both insulin sensitivity and ß-cell function (5.01% increase in HOMA2-%S and 4.01-6.28% increase in IGI/IR and ISSI-2 per SD increase in 20:0); 22:0 was positively associated with insulin sensitivity, with a 6.55% increase in HOMA2-%S and a 5.80% increase in ISI per SD increase in 22:0. Lastly, 24:0 was positively associated with insulin sensitivity and ß-cell function (7.94-8.45% increase in HOMA2-%S and ISI, and a 4.61-6.93% increase in IGI/IR and ISSI-2 per SD increase in 24:0). Fewer significant associations were observed in the cholesteryl ester and nonesterified pools. Overall, our results indicate positive longitudinal associations of VLCSFAs with insulin sensitivity and ß-cell function, especially within the triacylglycerol pool.

Evaluation of ethnic differences in cardiometabolic risk in children.

PURPOSE: In adults, cardiometabolic conditions manifest differently by ethnicity with South Asians particularly predisposed. Whether these differences arise in childhood remains narrowly explored. To address this evidence gap, we examined whether children of different ethnicities display differences in cardiometabolic risk (CMR). METHODS: A cross-sectional analysis was conducted among 5557 children (3-11 years). Multivariable linear regression models adjusted for age, sex, z-body mass index, and demographic factors were used to estimate differences in CMR outcomes between children with parents that self-reported European ancestry (reference group) and one of 13 other ethnicities (African, Arab, East Asian, Latin American, South Asian, Southeast Asian, Mixed Ethnicities, and Other). The primary outcome was a CMR score, calculated as the sum of age- and sex-standardized waist circumference, systolic blood pressure (SBP), glucose, log-triglycerides, and inverse high-density lipoprotein cholesterol (HDL-C), divided by √5. RESULTS: Lower mean CMR scores were observed among children with African (ß = -0.62, 95% CI: -0.92; -0.32) and East Asian (ß = -0.41, 95% CI: -0.68, -0.15) ancestry compared to children with European ancestry. Children with South Asian ancestry had higher SBP (ß = 2.25, 95% CI: 1.27, 3.22) and non-HDL-C (ß = 0.17, 95% CI: 0.07, 0.26) than children with European ancestry. CONCLUSIONS: Ethnic differences in CMR were observed in early and middle childhood.

Association of circulating branched chain fatty acids with insulin sensitivity and beta cell function in the PROMISE cohort.

Branched chain fatty acids (BCFAs) are mainly saturated fatty acids with a methyl branch on the penultimate or antepenultimate carbon atom. While BCFAs are endogenously produced via the catabolism of branched chain amino acids, the primary exogenous source of BCFAs in the human body is via the diet, including dairy products. Recently, BCFAs have been identified as having a potentially protective role in the etiology of cardiometabolic disorders although current literature is limited. We aimed to investigate the longitudinal associations of circulating BCFAs across four serum pools with insulin sensitivity, beta cell function, and glucose concentrations in the PROMISE Cohort. Estimates of insulin sensitivity were assessed using Matsuda's insulin sensitivity index (ISI) and the homeostasis model assessment of insulin sensitivity (HOMA2). Estimates of beta cell function were determined using the insulinogenic index divided by HOMA insulin resistance and the insulin secretion-sensitivity index-2 (ISSI-2). Baseline serum samples were analyzed for BCFAs using gas-chromatography flame ionization detection. Longitudinal associations were determined using generalized estimating equations. In the free fatty acid (FFA) pool, iso15:0 and anteiso15:0 were positively associated with logHOMA2 (iso15:0 logHOMA2-%S: ß = 6.86, 95% CI: [1.64, 12.36], p < 0.05, anteiso15:0 logHOMA2-%S: ß = 6.36, 95% CI: [0.63, 12.42], p < 0.05) while anteiso14:0 was inversely associated with measures of insulin sensitivity (iso14:0 logHOMA2-%S: ß = -2.35, 95% CI: [-4.26, -0.40], p < 0.05, logISI: ß = -2.30, 95% CI: [-4.32, -0.23], p < 0.05, anteiso14:0 logHOMA2-%S: ß = -4.72, 95% CI: [-7.81, -1.52], p < 0.05, logISI: ß = -6.13, 95% CI: [-9.49, -2.66], p < 0.01). Associations in other pools were less consistent. We identified the potential importance of specific BCFAs, specifically iso14:0, anteiso14:0, iso15:0, anteiso15:0, in cardiometabolic phenotypes underlying type 2 diabetes.

Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study.

BACKGROUND: Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the "intended substitution") versus water (the "standard of care substitution") for SSBs on glucose tolerance and microbiota diversity. DESIGN AND METHODS: The STOP Sugars NOW trial (NCT03543644) is a pragmatic, "head-to-head", open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle. BASELINE RESULTS: Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%). CONCLUSIONS: Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03543644.

Sugar-sweetened beverage consumption and weight gain in children and adults: a systematic review and meta-analysis of prospective cohort studies and randomized controlled trials.

BACKGROUND: Sugar-sweetened beverages (SSBs) have been implicated in fueling the obesity epidemic. OBJECTIVES: This study aimed to update a synthesis of the evidence on SSBs and weight gain in children and adults. METHODS: MEDLINE, Embase, and Cochrane databases were searched through September 8, 2022, for prospective cohort studies and randomized controlled trials (RCTs) that evaluated intake of SSBs in relation to BMI and body weight in children and adults, respectively. Eligible interventions were compared against a noncaloric control. Study-level estimates were pooled using random-effects meta-analysis and presented as ß-coefficients with 95% CIs for cohorts and weighted mean differences (MDs) with 95% CIs for RCTs. RESULTS: We identified 85 articles including 48 in children (40 cohorts, n = 91,713; 8 RCTs, n = 2783) and 37 in adults (21 cohorts, n = 448,661; 16 RCTs, n = 1343). Among cohort studies, each serving/day increase in SSB intake was associated with a 0.07-kg/m2 (95% CI: 0.04 kg/m2, 0.10 kg/m2) higher BMI in children and a 0.42-kg (95% CI: 0.26 kg, 0.58 kg) higher body weight in adults. RCTs in children indicated less BMI gain with SSB reduction interventions compared with control (MD: -0.21 kg/m2; 95% CI: -0.40 kg/m2, -0.01 kg/m2). In adults, randomization to addition of SSBs to the diet led to greater body weight gain (MD: 0.83 kg; 95% CI: 0.47 kg, 1.19 kg), and subtraction of SSBs led to weight loss (MD: -0.49 kg; 95% CI: -0.66 kg, -0.32 kg) compared with the control groups. A positive linear dose-response association between SSB consumption and weight gain was found in all outcomes assessed. CONCLUSIONS: Our updated systematic review and meta-analysis expands on prior evidence to confirm that SSB consumption promotes higher BMI and body weight in both children and adults, underscoring the importance of dietary guidance and public policy strategies to limit intake. This meta-analysis was registered at the International Prospective Register of Systematic Reviews as CRD42020209915.

The Environmental Sustainability of Plant-Based Dietary Patterns: A Scoping Review.

BACKGROUND: A large part of the existential threat associated with climate change is the result of current human feeding patterns. Over the last decade, research evaluating the diet-related environmental impacts of plant-based diets has emerged, and a synthesis of the available data is now due. OBJECTIVES: The objectives of the study were as follows: 1) to compile and summarize the literature on diet-related environmental impacts of plant-based dietary patterns; 2) to assess the nature of the data on impacts of plant-based dietary patterns on both environmental parameters and health (e.g., if land use is reduced for a particular diet, is cancer risk also reduced?); and 3) to determine where sufficient data exist for meta-analyses, in addition to identifying gaps within the literature. METHODS: Global peer-reviewed studies on the environmental impacts of plant-based diets were searched in Ovid MEDLINE, EMBASE, and Web of Science. After removing duplicates, the screening identified 1553 records. After 2 stages of independent review by 2 reviewers, 65 records met the inclusion criteria and were eligible to be used in synthesis. RESULTS: Evidence suggests that plant-based diets may offer lower greenhouse gas emissions (GHGEs), land use, and biodiversity loss than offered by standard diets; however, the impact on water and energy use may depend on the types of plant-based foods consumed. Further, the studies were consistent in demonstrating that plant-based dietary patterns that reduce diet-related mortality also promote environmental sustainability. CONCLUSIONS: Overall, there was agreement across the studies regarding the impact of plant-based dietary patterns on GHGE, land used, and biodiversity loss despite varied plant-based diets assessed.

Lifestyle Factors Associated with Circulating Very Long-Chain Saturated Fatty Acids in Humans: A Systematic Review of Observational Studies.

Recent observational studies have documented inverse associations of circulating very long-chain saturated fatty acids (VLCSFAs), namely arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), with cardiometabolic outcomes. In addition to their endogenous production, it has been suggested that dietary intake or an overall healthier lifestyle may influence VLCSFA concentrations; however, a systematic review of the modifiable lifestyle contributors to circulating VLCSFAs is lacking. Therefore, this review aimed to systematically assess the effects of diet, physical activity, and smoking on circulating VLCSFAs. Following registration on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42021233550), a systematic search of observational studies was conducted in MEDLINE, EMBASE, and The Cochrane databases up to February 2022. A total of 12 studies consisting of mostly cross-sectional analyses were included in this review. The majority of the studies documented the associations of dietary intake with total plasma or red blood cell VLCSFAs, in which a range of macronutrients and food groups were examined. Two cross-sectional analyses showed a consistent positive association between total fat and peanut intake with 22:0 and 24:0 and an inverse association between alcohol intake and 20:0 and 22:0. Furthermore, a moderate positive association between physical activity and 22:0 and 24:0 was observed. Lastly, there were conflicting results on the effects of smoking on VLCSFA. Although most studies had a low risk of bias; the findings of this review are limited by the bi-variate analyses presented in the majority of the included studies, therefore, the impact of confounding is unclear. In conclusion, although the current observational literature examining lifestyle determinants of VLCSFAs is limited, existing evidence suggests that circulating 22:0 and 24:0 may be influenced by higher total and saturated fat consumption and nut intake.

Treatment of Gestational Diabetes Mellitus and Maternal Risk of Diabetes After Pregnancy.

OBJECTIVE: To compare postpartum glucose tolerance between women treated for gestational diabetes mellitus (GDM) and those not treated. RESEARCH DESIGN AND METHODS: Metabolic testing was performed at 3 and 12 months postpartum in 599 women comprising the following gestational glucose tolerance groups: 1) normal glucose challenge test (GCT) and oral glucose tolerance test (OGTT) during pregnancy, 2) abnormal GCT with normal OGTT, 3) gestational impaired glucose tolerance, 4) mild untreated GDM, and 5) severe treated GDM. RESULTS: Birth weight progressively increased across groups 1-4 before falling steeply in treated GDM (P < 0.0001). In contrast, at 3 and 12 months, insulin sensitivity and ß-cell function progressively decreased across the five groups, mirrored by rising fasting and 2-h glucose (all P < 0.0001). Accordingly, prevalence of prediabetes/diabetes at 12 months increased in a stepwise manner across groups 1-5 (2.8%, 9.6%, 13.5%, 21.5%, and 32.6%, respectively; P < 0.0001). CONCLUSIONS: Treating GDM lowers birth weight but does not disrupt the association between gestational glycemia and maternal prediabetes/diabetes after pregnancy.

Association of branched chain fatty acids with cardiometabolic disorders in humans: a systematic review.

CONTEXT: Despite advances in treatments for cardiometabolic disorders such as type 2 diabetes mellitus and obesity, the increasing frequency of these conditions is of major clinical and public health concern. Therefore, primary prevention including diet and lifestyle approaches continues to play a key role in risk reduction. Meta-analyses of prospective cohort studies have documented inverse associations of dairy consumption with the incidence of different cardiometabolic disorders. Dairy is the largest dietary contributor of branched chain fatty acids (BCFAs), which have been suggested to not only serve as biomarkers of dairy consumption but may also have bioactive properties contributing to reducing the risk of cardiometabolic outcomes. To date, however, the literature on this topic has not been systematically reviewed. OBJECTIVE: The aim here was to report the results of a systematic review of the association of BCFAs with cardiometabolic disorders in humans. DATA SOURCES: Search terms were developed and run through the Ovid MEDLINE, Ovid Embase, and the Cochrane Library databases. DATA EXTRACTION: Articles were selected on the basis of prespecified inclusion criteria and assessed for risk of bias by independent reviewers. RESULTS: Four studies (n = 2 cross sectional; n = 1 randomized feeding trial and n = 1 pre-post study) were identified. Two studies reported significant inverse associations between serum BCFAs and insulin resistance, triglycerides and/or body mass index. One study identified an inverse association between adipose tissue monomethyl BCFAs and skeletal muscle insulin resistance. In contrast, the randomized feeding trial reported no significant differences to stool BCFA concentrations or body mass index in obese participants following assignment to fruit-vegetable or whole-grain diet groups compared with a refined-grain control group. CONCLUSIONS: Current evidence suggests beneficial associations of circulating BCFAs with cardiometabolic risk phenotypes, although data in human participants are limited, indicating that additional research is required. PROSPERO REGISTRATION NO: CRD42021224975.

The Portfolio Diet and Incident Type 2 Diabetes: Findings From the Women's Health Initiative Prospective Cohort Study.

OBJECTIVE: A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes. RESEARCH DESIGN AND METHODS: This analysis included 145,299 postmenopausal women free of diabetes at baseline in the Women's Health Initiative (WHI) Clinical Trials and Observational Study from 1993 to 2021. Adherence to the diet was assessed with a score based on six components (high in plant protein [soy and pulses], nuts, viscous fiber, plant sterols, and monounsaturated fat and low in saturated fat and cholesterol) determined from a validated food-frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association of the Portfolio Diet, alongside the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, with incident type 2 diabetes, with adjustment for potential confounders. RESULTS: Over a mean follow-up of 16.0 years, 13,943 cases of incident type 2 diabetes were identified. In comparisons of the highest with the lowest quintiles of adherence, the HRs for risk of incident type 2 diabetes were 0.77 (95% CI 0.72, 0.82) for the Portfolio Diet, 0.69 (0.64, 0.73) for the DASH diet, and 0.78 (0.74, 0.83) for the Mediterranean diet. These findings were attenuated by 10% after additional adjustment for BMI. CONCLUSIONS: Greater adherence to the plant-predominant Portfolio, DASH, and Mediterranean diets was prospectively associated with lower risk of type 2 diabetes in postmenopausal women.

Metabolomic profile of combined healthy lifestyle behaviours in humans: A systematic review.

A combination of healthy lifestyle behaviours (i.e., regular physical activity, nutritious diet, no smoking, moderate alcohol, and healthy body mass) has been consistently associated with beneficial health outcomes including reduced risk of cardiometabolic diseases. Metabolomic profiles, characterized by distinct sets of biomarkers, have been described for healthy lifestyle behaviours individually and in combination. However, recent literature calls for systematic evaluation of these heterogenous data to identify potential clinical biomarkers relating to a combined healthy lifestyle. The objective was to systematically review existing literature on the metabolomic profile of combined healthy lifestyle behaviours. MEDLINE, EMBASE and Cochrane databases were searched through March 2022. Studies in humans outlining the metabolomic profile of a combination of two or more healthy lifestyle behaviours were included. Collectively, the metabolomic profile following regular adherence to combined healthy lifestyle behaviours points to a positive association with beneficial fatty acids and phosphocreatine, and inverse associations with triglycerides, trimethylamine N-oxide, and acylcarnitines. The findings suggest that a unique metabolomic profile is associated with combined healthy lifestyle behaviours. Additional research is warranted to further describe this metabolomic profile using targeted and untargeted metabolomic approaches along with uniform definitions of combined healthy lifestyle variables across populations.

Treating Gestational Diabetes Reduces Birth Weight but Does Not Affect Infant Adiposity Across the 1st Year of Life.

OBJECTIVE: The continuum of maternal glycemia in pregnancy shows continuous associations with both 1) neonatal birth weight at delivery and 2) subsequent adiposity later in childhood. While treating gestational diabetes mellitus (GDM) can lower birth weight and thereby disrupt the former association, it is unclear if such treatment reduces childhood adiposity. Thus, we sought to compare anthropometry across the 1st year of life between infants born to women who were treated for GDM and those with lesser degrees of gestational dysglycemia (untreated). RESEARCH DESIGN AND METHODS: Anthropometric measurements were performed at 3 months and 12 months of life in 567 infants born to women comprising the following four gestational glucose tolerance groups: 1) women with normoglycemia on both glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy; 2) women with an abnormal GCT but normal OGTT; 3) those with mild gestational impaired glucose tolerance; and 4) women treated for GDM. RESULTS: Birth weight progressively increased across the three untreated groups but was lowest in women treated for GDM (P = 0.0004). Similarly, women treated for GDM had the lowest rate of macrosomia (P = 0.02). Conversely, however, there were no differences among the four groups in weight z score, length z score, weight-for-length z score, or BMI z score at either 3 months or 12 months (all P values = NS). Similarly, there were no differences among the groups in triceps/biceps/subscapular/suprailiac skinfold thickness or sum of skinfolds at either 3 months or 12 months (all P values = NS). CONCLUSIONS: Despite reducing birth weight and macrosomia, the treatment of GDM does not have analogous effects on infant adiposity across the 1st year of life.

Associations of Metabolic and Obstetric Risk Parameters with Timing of Lactogenesis II.

Lactogenesis II is the onset of copious milk production following parturition. Delayed onset of lactogenesis II (DLII) often contributes to poorer lactation performance, which may adversely affect maternal and child health. The present study aims to identify the metabolic and obstetric risk factors for DLII in a secondary analysis of a prospective cohort study following pregnant women through postpartum. We defined the onset of lactogenesis II as delayed if it occurred ≥72 h postpartum. Multiple logistic regression analyses were conducted to evaluate the associations of metabolic and obstetric variables with DLII. Median onset of lactogenesis II was 72.4 h (IQR 60.4-91.6) postpartum, and 55.4% (98 of 177) of women experienced DLII. Time to first breast contact ≥ 2 h postpartum compared to ≤1 h postpartum was associated with DLII (OR 2.71 95% CI 1.12-6.53) with adjustment for age, race, pregravid BMI, primiparity, and mode of delivery, while metabolic variables were not significantly associated with DLII. In this comprehensive examination of potential metabolic and obstetric parameters, earlier timing of putting the infant to the breast remained significantly associated with earlier onset of milk coming in after consideration of the other potential risk factors. Obstetrical practices, including putting the baby to the breast later, may have an important impact on the timing of lactation, and interventions are needed to address this concern.