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Objective: A common approach to screening for gestational diabetes mellitus (GDM) is the universal testing of all pregnant women with a 1-h, 50-g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) in those in whom the GCT is positive (≥7.8 mmol/L). More important, the GCT is performed at any time of day, but there has been limited study of the effect of time of day on test performance. Thus, using their subsequent OGTT (performed in the morning), we sought to characterize the metabolic function of women with positive GCTs in relation to the timing of their test.Research Design and Methods: A total of 927 women with positive GCTs underwent a 3-h 100-g OGTT. They were stratified into four groups by time of day (hours) of their GCT: <0900 (n = 171), 0900-1059 (n = 288), 1100-1259 (n = 189), and ≥1300 (n = 279).Results: On the OGTT, the prevalence of GDM progressively decreased across the GCT groups from <0900 h (26.9%) to 0900-1059 h (25.0%) to 1100-1259 h (21.7%) to ≥1300 h (21.5%; P = 0.0022). After adjustment for GDM risk factors, mean adjusted glucose area under the curve (AUC(gluc)) similarly decreased across the groups, while insulin sensitivity (Matsuda index) and β-cell function (Insulin Secretion-Sensitivity Index-2) progressively increased (all P < 0.0001). In particular, compared with the <0900- and 0900-1059-h groups, women whose positive GCT occurred after 1300 h had superior metabolic function, as evidenced by lower AUC(gluc), higher insulin sensitivity, and better β-cell function (all P ≤ 0.0097).Conclusions: Among women with a positive GCT, those tested in the afternoon have better metabolic function and a lower risk of GDM on subsequent OGTT. [ABSTRACT FROM AUTHOR]

OBJECTIVE The increased risk of type 2 diabetes in women with glucose intolerance in pregnancy is mediated by deterioration of their β-cell function, which occurs as early as the first year postpartum. We thus sought to identify early determinants of their declining β-cell function. RESEARCH DESIGN AND METHODS Women with recent gestational glucose intolerance (166) underwent oral glucose tolerance test at 3 and 12 months postpartum. They were stratified into those in whom β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) declined over this time (decliners; n = 92) and those in whom it did not (nondecliners; n = 74). RESULTS Between 3 and 12 months, hepatic insulin sensitivity (1/homeostasis model assessment of insulin resistance [HOMA-IR]) decreased in decliners but not in nondecliners. Over this time, the change in 1/HOMA-IR emerged as an independent predictor of the change in ISSI-2 (t = 5.5; P < 0.0001). Increased hepatic insulin sensitivity independently predicted a lower likelihood of declining β-cell function (odds ratio = 0.13 [95% CI 0.06-0.29]; P < 0.0001). CONCLUSIONS Hepatic insulin resistance is an early determinant of declining β-cell function after gestational dysglycemia. [ABSTRACT FROM AUTHOR]

Objective: To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), β-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes.Research Design and Methods: We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (IS(OGTT)) and the homeostasis model assessment of IR (HOMA-IR), β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUC(glucose)). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI.Results: Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up IS(OGTT) or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (β = 0.005, P = 0.015) and ISSI-2 (β = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUC(glucose) (β = -0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53-0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59-1.02]).Conclusions: Higher baseline 25(OH)D independently predicted better β-cell function and lower AUC(glucose) at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology. [ABSTRACT FROM AUTHOR]

Objective: A recent meta-analysis of 13 prospective studies reported that higher levels of adiponectin were significantly associated with lower risk of type 2 diabetes. Most previous studies, however, were limited in their ability to adjust for appropriate confounding variables. Our objective, therefore, was to study this association after adjustment for directly measured adiposity and insulin sensitivity, expressed as the insulin sensitivity index (S(I)).Research Design and Methods: The study included 1,096 Hispanic and African American participants free of diabetes at baseline (2000-2002) who returned for follow-up after 5 years. S(I) was determined from frequently sampled intravenous glucose tolerance tests with minimal model analysis. Visceral adipose tissue (VAT) area was determined by computed tomography. Diabetes and impaired fasting glucose (IFG) were defined using American Diabetes Association criteria. Multivariate generalized estimating equation logistic regression models were used to account for correlations within families.Results: A total of 82 subjects met criteria for incident diabetes. After adjustment for age, sex, ethnicity, and smoking, adiponectin was significantly inversely associated with diabetes (odds ratio [OR] 0.54 per 1 SD difference [95% CI 0.38-0.76]). The association remained significant after additional adjustment in individual models for BMI, homeostasis model assessment of insulin resistance, or VAT (all P < 0.05). However, adiponectin was no longer associated in separate models adjusted for S(I) or IFG (OR 0.81 [0.56-1.16] and 0.75 [0.53-1.06], respectively).Conclusions: Adiponectin was inversely associated with incident diabetes after adjustment for conventional anthropometric and metabolic variables or VAT. Adjustment for detailed measures of S(I) attenuated this relationship, however, suggesting that the link between adiponectin and diabetes may operate at least in part through insulin resistance. [ABSTRACT FROM AUTHOR]

Objective: Glucose effectiveness (S(G)), the capacity of glucose to enhance its own disposition, is an independent predictor of future diabetes. However, there are data on cross-sectional and longitudinal changes of S(G) and its components, basal insulin effect on S(G) (BIE) and S(G) at zero insulin (GEZI), but the natural course of S(G) has not been described in a large population.Research Design and Methods: S(G) was measured at baseline in 1,265 participants (aged 40-69 years) and at the 5-year examination in 827 participants in the Insulin Resistance Atherosclerosis Study (IRAS) using the frequently sampled intravenous glucose tolerance test. None of these participants were treated with glucose-lowering agents.Results: In cross-sectional analyses, S(G), BIE, and GEZI deteriorated with worsening of glucose tolerance (P < 0.001 for all three associations). In longitudinal analyses among subjects with normal glucose tolerance (NGT) at baseline, S(G), BIE, and GEZI declined in those who progressed to impaired glucose tolerance (IGT) or diabetes (P < 0.001 for all three measures). More modest longitudinal changes were demonstrated in individuals with IGT. The transition back to NGT (as opposed to no change) compared with the transition to diabetes was statistically significant for S(G) (P = 0.049) and BIE (P = 0.042) and was not a statistically significant trend for GEZI (P = 0.332). In individuals with diabetes, only BIE had a significant decline (P = 0.003).Conclusions: S(G), BIE, and GEZI decline in subjects whose glycemic status worsens. S(G) and GEZI deteriorate more in the initial stages of the disease process. [ABSTRACT FROM AUTHOR]

Objective: In the Canadian Normoglycemia Outcome Evaluation (CANOE) trial, low-dose rosiglitazone/metformin reduced the risk of diabetes in subjects with impaired glucose tolerance by 66% over a median of 3.9 years. We evaluate the temporal changes in glycemic control, insulin sensitivity, and β-cell function during this trial.Research Design and Methods: CANOE participants (n=207) underwent annual oral glucose tolerance testing, enabling temporal comparison of glycemia, insulin sensitivity (Matsuda index), and β-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) between the rosiglitazone/metformin and placebo arms.Results: Glycemic parameters and insulin sensitivity improved in the rosiglitazone/metformin arm in year 1, but deteriorated in the years thereafter as in the placebo arm. Generalized estimating equation analysis confirmed that both insulin sensitivity and β-cell function decreased over time (Matsuda: β=-0.0515, P<0.0001; ISSI-2: β=-6.6507, P<0.0001), with no significant time-by-treatment interaction (Matsuda: P=0.57; ISSI-2: P=0.22).Conclusions: Despite preventing incident diabetes, low-dose rosiglitazone/metformin did not modify the natural history of worsening insulin resistance and β-cell dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Disposition index (DI) and glucose effectiveness (S(G)) are risk factors for diabetes. However, the effect of DI and S(G) on future diabetes has not been examined in large epidemiological studies using direct measures.Research Design and Methods: Insulin sensitivity index (S(I)), acute insulin response (AIR), and S(G) were measured in 826 participants (aged 40-69 years) in the Insulin Resistance Atherosclerosis Study (IRAS) by the frequently sampled intravenous glucose tolerance test. DI was expressed as S(I) x AIR. At the 5-year follow-up examination, 128 individuals (15.5%) had developed diabetes.Results: The area under the receiver operating characteristic curve of a model with S(I) and AIR was similar to that of DI (0.767 vs. 0.774, P = 0.543). In a multivariate logistic regression model that included both DI and S(G), conversion to diabetes was predicted by both S(G) (odds ratio x 1 SD, 0.61 [0.47-0.80]) and DI (0.68 [0.54-0.85]) after adjusting for demographic variables, fasting and 2-h glucose concentrations, family history of diabetes, and measures of obesity. Age, sex, race/ethnicity, glucose tolerance status, obesity, and family history of diabetes did not have a significant modifying impact on the relation of S(G) and DI to incident diabetes.Conclusions: The predictive power of DI is comparable to that of its components, S(I) and AIR. S(G) and DI independently predict conversion to diabetes similarly across race/ethnic groups, varying states of glucose tolerance, family history of diabetes, and obesity. [ABSTRACT FROM AUTHOR]

Objective: A1C is an optional method for diagnosing diabetes and also for detecting individuals at increased risk of the disease. However, how A1C compares with fasting (FPG) and 2-h plasma glucose for detecting at-risk individuals is not well known.Research Design and Methods: A 2-h glucose tolerance test, frequently sampled intravenous glucose tolerance test, and A1C were obtained at the follow-up examination in 855 participants in the Insulin Resistance Atherosclerosis Study (IRAS). For this report, 385 individuals were at increased risk of diabetes as defined by A1C between 5.7 and 6.4%, impaired glucose tolerance (IGT), and/or impaired fasting glucose (IFG).Results: IFG and IGT identified 69.1 and 59.5% of all individuals at increased risk of diabetes, respectively. A1C 5.7-6.4% detected 23.6% of all at-risk individuals, although more African Americans (31.4%) and Hispanics (35.2%) than non-Hispanic whites (9.9%). Relative to A1C, FPG was more strongly related to fasting insulin (r = 0.38 vs. 0.26; P < 0.01), acute insulin response (r = - 0.20 vs. - 0.09; P < 0.01), and waist circumference (r = 0.43 vs. 0.25; P < 0.001) by the Spearman correlation test. Similarly, 2-h plasma glucose was more strongly related to Si (r = - 0.40 vs. - 0.27; P < 0.01) and triglycerides (r = 0.30 vs. 0.08; P < 0.001).Conclusions: A1C 5.7-6.4% is less sensitive for detecting at-risk individuals than IFG and IGT, particularly among non-Hispanic whites. Single determinations of FPG and 2-h plasma glucose seem to be more precise correlates of insulin resistance and secretion than A1C and, in general, better for other metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective: Both gestational diabetes mellitus (GDM) and mild glucose intolerance in pregnancy identify women at increased risk of future type 2 diabetes. In this context, we queried whether metabolic changes that occur in the 1st year postpartum vary in relation to gestational glucose tolerance status.Research Design and Methods: Three-hundred-and-ninety-two women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy followed by repeat OGTT at both 3 months' postpartum and 12 months' postpartum. The antepartum testing defined four gestational glucose tolerance groups: GDM (n = 107); gestational impaired glucose tolerance (GIGT) (n = 75); abnormal GCT with normal glucose tolerance (NGT) on OGTT (abnormal GCT NGT) (n = 137); and normal GCT with NGT on OGTT (normal GCT NGT) (n = 73).Results: The prevalence of dysglycemia progressively increased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM at both 3 months' postpartum (2.7% to 10.2% to 18.7% to 34.6%, P < 0.0001) and 12 months' postpartum (2.7% to 11.7% to 17.3% to 32.7%, P < 0.0001). Between 3 and 12 months' postpartum, the groups did not differ with respect to changes in waist circumference, weight, or insulin sensitivity. Importantly, however, they exhibited markedly different changes in beta-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) (P = 0.0036), with ISSI-2 declining in both the GDM and GIGT groups. Furthermore, on multiple linear regression analysis, both GDM (t = -3.06, P = 0.0024) and GIGT (t = -2.18, P = 0.03) emerged as independent negative predictors of the change in ISSI-2 between 3 and 12 months' postpartum.Conclusions: Women with GDM and GIGT exhibit declining beta-cell function in the 1st year postpartum that likely contributes to their future diabetic risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE The objective of this study was to determine the degree to which ramipril and/or rosiglitazone changed beta-cell function over time among individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) who participated in the Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication (DREAM) Trial, which evaluated whether ramipril and/or rosiglitazone could prevent or delay type 2 diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS The present analysis included subjects (n = 982) from DREAM trial centers in Canada who had oral glucose tolerance tests at baseline, after 2 years, and at the end of the study. beta-Cell function was assessed using the fasting proinsulin-to-C-peptide ratio (PI/C) and the insulinogenic index (defined as 30-0 min insulin/30-0 min glucose) divided by homeostasis model assessment of insulin resistance (insulinogenic index [IGI]/insulin resistance [IR]). RESULTS Subjects receiving rosiglitazone had a significant increase in IGI/IR between baseline and end of study compared with the placebo group (25.59 vs. 1.94, P < 0.0001) and a significant decrease in PI/C (-0.010 vs. -0.006, P < 0.0001). In contrast, there were no significant changes in IGI/IR or PI/C in subjects receiving ramipril compared with placebo (11.71 vs. 18.15, P = 0.89, and -0.007 vs. -0.008, P = 0.64, respectively). The impact of rosiglitazone on IGI/IR and PI/C was similar within subgroups of isolated IGT and IFG + IGT (all P < 0.001). Effects were more modest in those with isolated IFG (IGI/IR: 8.95 vs. 2.13, P = 0.03; PI/C: -0.003 vs. -0.001, P = 0.07). CONCLUSIONS Treatment with rosiglitazone, but not ramipril, resulted in significant improvements in measures of beta-cell function over time in pre-diabetic subjects. Although the long-term sustainability of these improvements cannot be determined from the present study, these findings demonstrate that the diabetes preventive effect of rosiglitazone was in part a consequence of improved beta-cell function. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate associations of adiponectin, leptin, C-reactive protein (CRP), interleukin (IL)-6, and serum amyloid A (SAA), individually or in combinations, with risk of incident type 2 diabetes in a Aboriginal Canadian [corrected] population.Research Design and Methods: Of the 606 Sandy Lake Health and Diabetes Project cohort subjects who were free of diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments. Concentrations of fasting adiponectin, leptin, CRP, IL-6, SAA, and covariates were measured at baseline. Fasting glucose and a 75-g oral glucose tolerance test were obtained at baseline and follow-up to determine incident type 2 diabetes, defined as clinically diagnosed type 2 diabetes or as fasting plasma glucose > or =7.0 mmol/l or 2-h postload plasma glucose > or =11.1 mmol/l at follow-up.Results: Low adiponectin, high leptin, and low adiponectin-to-leptin ratio at baseline were associated with increased risk of incident type 2 diabetes after adjustment for age, sex, triglycerides, HDL cholesterol, hypertension, and impaired glucose tolerance (odds ratio 0.63 [95% CI 0.48-0.83], 1.50 [1.02-2.21], and 0.54 [0.37-0.77], respectively). When the models were additionally adjusted for waist circumference or BMI, however, only low adiponectin remained significantly associated with increased incident diabetes (0.68 [0.51-0.90]). Combinations of leptin, CRP, IL-6, and/or SAA with adiponectin, assessed using either the ratio or joint effects, did not improve diabetes prediction.Conclusions: Low baseline adiponectin is associated with increased risk of incident type 2 diabetes independent of leptin, CRP, IL-6, SAA, and metabolic syndrome variables including obesity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Methods to assess beta-cell function in clinical studies are limited. The aim of the current study was to compare a direct measure of insulin secretion with fasting surrogate markers in relation to glucose tolerance status. RESEARCH DESIGN AND METHODS: In 1,380 individuals from the Insulin Resistance Atherosclerosis Study, beta-cell function was assessed using a frequently sampled intravenous glucose tolerance test (first-phase insulin secretion; acute insulin response [AIR]), homeostasis model assessment of beta-cell function (HOMA-B), proinsulin levels, and the proinsulin-to-insulin ratio. Beta-cell function was cross-sectionally analyzed by glucose tolerance categories (normal glucose tolerance [NGT], n = 712; impaired glucose tolerance [IGT], n = 353; newly diagnosed diabetes by 2-h glucose from an oral glucose tolerance test [OGTT] [DM2h], n = 80; newly diagnosed diabetes by fasting glucose [DMf], n = 135; or newly diagnosed diabetes by fasting and 2-h glucose and established diabetes on diet/exercise only [DM], n = 100). RESULTS: In Spearman correlation analyses, proinsulin and the proinsulin-to-insulin ratio were only modestly inversely related to AIR (r values from -0.02 to -0.27), and AIR was strongly related to HOMA-B (r values 0.56 and 0.58). HOMA-B markedly underestimated the magnitude of the beta-cell defect across declining glucose tolerance, especially for IGT and new DM by OGTT compared with AIR. Analyses adjusting for insulin sensitivity showed that beta-cell function was compromised in IGT, DM2h, DMf, and DM, relative to NGT, by 13, 12, 59, and 62% (HOMA-B) and by as much as 40, 60, 80, and 75%, using AIR. CONCLUSIONS: Subjects with IGT and early-stage, asymptomatic type 2 diabetic patients have more pronounced beta-cell defects than previously estimated from epidemiological studies using homeostasis model assessment. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that tobacco is a well-recognized risk factor for pancreatic cancer, no study has yet reported on the association between environmental tobacco smoke (ETS) and this malignancy. We investigated the relationship between pancreatic cancer and childhood and adult exposure to ETS using a case-control study design.Methods: Our study population consisted of 583 pancreatic cancer cases and 4,813 population-based controls that were identified within 8 Canadian provinces between 1994 and 1997. Mail-out questionnaires were used to collect risk factor information and a lifetime residential and occupational history of exposure to ETS.Results: Among never smokers, those who were exposed to ETS both as a child and as an adult had an odds ratio of 1.21 (95% CI=0.60-2.44) relative to those with no exposure. For active smoking, when the referent group consisted of never smokers who had not been regularly exposed to ETS, the risk increases were more pronounced with an increased number of years of smoking, cigarette pack-years, years since quit smoking, and average number of cigarettes smoked daily.Conclusions: Overall, our results are suggestive of a weak association between pancreatic cancer and ETS. Perhaps more importantly, they suggest that ETS smoking exposures may confound the risk of pancreatic cancer associated with active smoking measures commonly used in epidemiologic studies. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance.Research Design and Methods: We measured insulin sensitivity index (S(I)), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study.Results: MCRI was positively related to S(I) and negatively to AIR and adiposity across sex, race/ethnicity populations, and varying states of glucose tolerance, adiposity, and family history of diabetes. Differences in MCRI by race/ethnicity (lower in African Americans and Hispanics compared with non-Hispanic whites) and glucose tolerance were largely explained by differences in adiposity, S(I), and AIR.Conclusions: Insulin sensitivity, insulin secretion, and adiposity are correlates of insulin clearance and appear to explain differences in insulin clearance by race/ethnicity and glucose tolerance status. [ABSTRACT FROM AUTHOR]

Objective: The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM.Research Design and Methods: In total, 104 full-term, singleton infants born to women with (n = 36) and without (n = 68) GDM were evaluated at age 1 year, with insulin resistance assessed by homeostasis model (HOMA-IR).Results: HOMA-IR at 1 year did not differ between infants born to mothers with and without GDM (P = 0.74). The sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year was the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039).Conclusions: In the 1st year of life, weight gain in infants born to women with GDM is associated with insulin resistance, unlike in their peers. [ABSTRACT FROM AUTHOR]

Objective: To examine cross-sectional associations of serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration with insulin resistance (IR) and beta-cell dysfunction in 712 subjects at risk for type 2 diabetes.Research Design and Methods: Serum 25(OH)D was determined using a chemiluminescence immunoassay. Insulin sensitivity/resistance were measured using the Matsuda insulin sensitivity index for oral glucose tolerance tests (IS(OGTT)) and homeostasis model assessment of insulin resistance HOMA-IR. beta-Cell function was determined using both the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). RESULTS Linear regression analyses indicated independent associations of 25(OH)D with IS(OGTT) and HOMA-IR (beta = 0.004, P = 0.0003, and beta = -0.003, P = 0.0072, respectively) and with IGI/IR and ISSI-2 (beta = 0.004, P = 0.0286, and beta = 0.003, P = 0.0011, respectively) after adjusting for sociodemographics, physical activity, supplement use, parathyroid hormone, and BMI.Conclusions: Vitamin D may play a role in the pathogenesis of type 2 diabetes, as 25(OH)D concentration was independently associated with both insulin sensitivity and beta-cell function among individuals at risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To compare different anthropometric measures in terms of their ability to predict type 2 diabetes and to determine whether predictive ability was modified by ethnicity.Research Design and Methods: Anthropometry was measured at baseline for 1,073 non-Hispanic white (nHW), African American (AA), and Hispanic (HA) subjects, of whom 146 developed type 2 diabetes after 5.2 years. Logistic regression models were used with areas under the receiver operator characteristic curve (AROCs) comparing the prediction of models.Results: Waist-to-height ratio (AROC 0.678) was the most predictive measure, followed by BMI (AROC 0.674). Results were similar in nHW and HA subjects, although in AA subjects, central adiposity measures appeared to best predict type 2 diabetes.Conclusions: Measures of central and overall adiposity predicted type 2 diabetes to a similar degree, except in AA subjects, for whom results suggested that central measures were more predictive. [ABSTRACT FROM AUTHOR]

Context: Lactation is associated with lower future risk of cardiovascular disease in women but the mechanism(s) underlying this relationship remain unclear., Objective: We sought to characterize the relationship between duration of exclusive breastfeeding and cardiovascular risk factors over the first 5-years postpartum., Design/setting/patients: In this prospective cohort study, 328 women underwent serial cardiometabolic characterization (anthropometry, blood pressure, lipids, fasting glucose, adiponectin, C-reactive protein (CRP)) at 1-year, 3-years, and 5-years postpartum., Outcome: Cardiovascular risk factors in 3 groups defined by duration of exclusive breastfeeding, as follows: <3 months (n=107), 3-6 months (n=101), and ≥6 months (n=120)., Results: The prevalence of metabolic syndrome did not differ between the groups at 3-years but, by 5-years postpartum, was higher in women who had exclusively breastfed <3 months than in those who did so for 3-6 and ≥6 months, respectively (14.0% vs 6.9% vs 4.2%; p=0.02). However, after adjustment for covariates (including BMI), there were no significant differences between groups in blood pressure, glucose, LDL cholesterol, HDL cholesterol, triglycerides or adiponectin. Indeed, the only cardiovascular risk factor difference that persisted after covariate adjustment was that women who had exclusively breastfed <3 months had higher CRP at both 3-years (p=0.04) and 5-years (p=0.01). Moreover, generalized estimating equation analyses with adjustment for covariates (including time-dependent BMI) showed that CRP remained higher over time in these women, as compared to their peers, from 1-year to 3-years to 5-years postpartum (p=0.03)., Conclusion: Sustained reduction of subclinical inflammation may contribute to the cardioprotective effect of lactation in women., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objectives: Although pre-clinical studies have shown a beneficial impact of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on adipose (AT) inflammation, the current literature from human studies is limited. Therefore, we aimed to evaluate the longitudinal associations of circulating levels of n-3 PUFAs with biomarkers of AT inflammation., Methods: Longitudinal data from participants in the PROMISE cohort (n = 474) were used. AT inflammation was measured using circulating biomarkers at baseline and up to 2 follow-up visits. n-3 PUFAs were measured at baseline in four serum lipid fractions. Generalized estimating equations (GEE) analyses evaluated longitudinal associations between n-3 PUFAs and AT inflammation, adjusting for covariates., Results: Fully adjusted GEE models indicated that higher baseline proportions of eicosapentaenoic acid (EPA), n-3 docosapentaenoic acid (n-3 DPA), and docosahexaenoic acid (DHA) in total serum were significantly inversely associated with longitudinal change in soluble CD163 (sCD163) (all p < 0.05). A significant positive association of n-3 DPA and DHA with longitudinal change in adiponectin (p < 0.05) was also observed. Generally consistent associations were observed between n-3 PUFAs and sCD163 and adiponectin in the four lipid fractions., Conclusions: These findings will add to the limited evidence on the potential role n-3 PUFAs have in the prevention and management of AT inflammation in humans and may help inform future interventions targeting chronic inflammation at the level of AT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

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/m 2 ), highest in undiagnosed GDM (1.23 ± 0.38 kg/m 2 ) and intermediate in non-GDM (0.89 ± 0.22 kg/m 2 ) (overall p = .04)., Conclusion: Diagnosis of GDM leads to increased physical activity after pregnancy that may partially attenuate postpartum weight retention., (© 2023 John Wiley & Sons Ltd.)

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/m 2 , 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., (© 2024. The Author(s).)

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 β 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.

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 (β = 30.67 and β = 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

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., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

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 β-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 β-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 β-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 β-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 β-cell function, especially within the triacylglycerol pool., (© 2023 by the American Diabetes Association.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 (β = -0.62, 95% CI: -0.92; -0.32) and East Asian (β = -0.41, 95% CI: -0.68, -0.15) ancestry compared to children with European ancestry. Children with South Asian ancestry had higher SBP (β = 2.25, 95% CI: 1.27, 3.22) and non-HDL-C (β = 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Tinajero has received funding from the Canadian Institutes of Health Research Canada Graduate Scholarship, University of Toronto. V. Malik has received funding from the Canada Research Chairs Program; Connaught New Researcher Award, University of Toronto; The Joannah & Brian Lawson Centre for Child Nutrition, University of Toronto; Temerity Faculty of Medicine Pathway Grant, University of Toronto; Canada Foundation for Innovation; and Ontario Research Fund and serves on the Canadian Institutes of Health Research Institute Advisory Board for Nutrition, Metabolism and Diabetes. J. Sievenpiper has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research (CIHR), Diabetes Canada, American Society for Nutrition (ASN), International Nut and Dried Fruit Council (INC) Foundation, National Honey Board (U.S. Department of Agriculture [USDA] honey “Checkoff” program), Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, Quaker Oats Center of Excellence, The United Soybean Board (USDA soy “Checkoff” program), The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), The Plant Protein Fund at the University of Toronto (a fund which has received contributions from IFF), and The Nutrition Trialists Network Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received food donations to support randomized controlled trials from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, Danone, Nutrartis, and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from ASN, Danone, Dairy Farmers of Canada, FoodMinds LLC, Nestlé, Abbott, General Mills, Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, International Sweeteners Association, and International Glutamate Technical Committee. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, Phynova, and Inquis Clinical Research. He is a former member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid member of the Board of Trustees and an unpaid scientific advisor for the Carbohydrates Committee of IAFNS. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. C. Birken has received funding from the Canadian Institutes of Health Research; Heart & Stroke Foundation of Canada; Physician Services Inc; The Edwin S.H. Leong Centre for Healthy Children, University of Toronto and Hospital for Sick Children; Centre for Addiction and Mental Health, Walmart Canada Regional Community Grant. J. Maguire and L. Anderson have received funding from the Canadian Institutes of Health Research. A. Hanley has received funding from an Investigator initiated research grant from the Dairy Farmers of Canada. None of the other authors declare any conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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: β = 6.86, 95% CI: [1.64, 12.36], p < 0.05, anteiso15:0 logHOMA2-%S: β = 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: β = -2.35, 95% CI: [-4.26, -0.40], p < 0.05, logISI: β = -2.30, 95% CI: [-4.32, -0.23], p < 0.05, anteiso14:0 logHOMA2-%S: β = -4.72, 95% CI: [-7.81, -1.52], p < 0.05, logISI: β = -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., (© 2023 The Authors. Lipids published by Wiley Periodicals LLC on behalf of AOCS.)

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., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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 β-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., (© 2023 by the American Diabetes Association.)

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/m 2 ) 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.

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 Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 β-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/m 2 (95% CI: 0.04 kg/m 2 , 0.10 kg/m 2 ) 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/m 2 ; 95% CI: -0.40 kg/m 2 , -0.01 kg/m 2 ). 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., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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., (© 2022 by the American Diabetes Association.)

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., (© 2022 Wiley-VCH GmbH.)

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is inversely associated with type 2 diabetes mellitus (T2DM) risk. Metabolic changes due to DASH adherence and their potential relationship with incident T2DM have not been described. The objective is to determine metabolite clusters associated with adherence to a DASH-like diet in the Insulin Resistance Atherosclerosis Study cohort and explore if the clusters predicted 5-year incidence of T2DM. The current study included 570 non-diabetic multi-ethnic participants aged 40–69 years. Adherence to a DASH-like diet was determined a priori through an eighty-point scale for absolute intakes of the eight DASH food groups. Quantitative measurements of eighty-seven metabolites (acylcarnitines, amino acids, bile acids, sterols and fatty acids) were obtained at baseline. Metabolite clusters related to DASH adherence were determined through partial least squares (PLS) analysis using R. Multivariable-adjusted logistic regression was used to explore the associations between metabolite clusters and incident T2DM. A group of acylcarnitines and fatty acids loaded strongly on the two components retained under PLS. Among strongly loading metabolites, a select group of acylcarnitines had over 50 % of their individual variance explained by the PLS model. Component 2 was inversely associated with incident T2DM (OR: 0·89; (95 % CI 0·80, 0·99), P -value = 0·043) after adjustment for demographic and metabolic covariates. Component 1 was not associated with T2DM risk (OR: 1·02; (95 % CI 0·88, 1·19), P -value = 0·74). Adherence to a DASH-type diet may contribute to reduced T2DM risk in part through modulations in acylcarnitine and fatty acid physiology.

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., (© 2022 by the American Diabetes Association.)

The recent coronavirus disease 2019 (COVID-19) pandemic has warranted the need to investigate potential therapies or prophylaxis against this infectious respiratory disease. There is emerging evidence about the potential role of nutrients on COVID-19 in addition to using medications such as hydroxychloroquine and azithromycin. This scoping review aims to explore the literature evaluating the effect of immunomodulatory nutrients on the outcomes including hospitalization, intensive care unit admission, oxygen requirement, and mortality in COVID-19 patients. A literature search of databases including Medline, EMBASE, CINAHL, Web of Science, Cochrane, Scopus, and PubMed, as well as hand-searching in Google Scholar (up to 10 February 2021) was conducted. All human studies with different study designs and without limitation on publication year were included except for non-English-language and review articles. Overall, out of 4412 studies, 19 met our inclusion criteria. Four studies examined the impact of supplementation with vitamin C, 4 studies - zinc, 8 studies - vitamin D, and 3 studies investigated the combination of 2 (zinc and vitamin C) or 3 (vitamin D, vitamin B-12, and magnesium) nutrients. Although limited data exist, available evidence demonstrated that supplementation with immune-supportive micronutrients such as vitamins D and C and zinc may modulate immunity and alleviate the severity and risk of infection. The effectiveness of vitamin C, vitamin D, and zinc on COVID-19 was different based on baseline nutrient status, the duration and dosage of nutrient therapy, time of administration, and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. This review indicated that supplementation with high-dose vitamin C, vitamin D, and zinc may alleviate the complications caused by COVID-19, including inflammatory markers, oxygen therapy, length of hospitalization, and mortality; however, studies were mixed regarding these effects. Further randomized clinical trials are necessary to identify the most effective nutrients and the safe dosage to combat SARS-CoV-2., (Copyright © 2021 © The Author(s) 2021. Published by Oxford University Press. Published by Elsevier Inc. All rights reserved.)

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.