Measures Of Metabolic Health Research Articles

TNF-alpha Concentrations in Serum and Human Milk of Mothers With Insufficient Versus Sufficient Milk Production

ObjectivesObesity and poor metabolic health are associated with poor lactation outcomes, potentially driven by elevated tumor necrosis factor alpha (TNF-α) from chronic inflammation. TNF-α reduces lipoprotein lipase (LpL) activity, limiting triglyceride (TG) uptake by the mammary gland for milk synthesis. Our objective here is to determine if TNF-α concentrations in serum and milk are higher in mothers with severely low compared to sufficient milk production and if TNF-α is associated with plasma TG. MethodsMothers screened for low milk production were categorized into very low (VL; 177 [87,219] mL/d; n = 23) and moderately low/normal (ML; Median [IQR]: 467 [373,655] mL/d; n = 20) milk production. An external control group had sufficient milk production (EC; 783 [717,818] mL/d; n = 18). Mothers provided a spot milk sample at a morning clinic visit, where fasting blood samples were taken for clinical metabolic health measures. TNF-α concentrations were measured in duplicate by high-sensitivity ELISA in serum and aqueous milk. Group differences were assessed by Wilcoxon Rank Sums Tests or Fisher’s Exact Chi Square Test (α = 0.05). Correlations were assessed by Spearman rank order. ResultsMothers were 31.3 [27.3, 34.1] years old, delivered at gestational age of 39.4 [38.6, 40.3] weeks, and were 43 [35, 56] days postpartum, with no significant differences among groups. Milk TNF-α was detected in 47% of samples (1.3 [0.8, 2.2] pg/mL). The proportion of detectable TNF-α (D-TNF) in milk was higher in VL compared with ML and EC (71%, 32%, 33% respectively; p = 0.02). Compared to undetected (U-TNF), subjects with D-TNF in milk had higher plasma TG (D-TNF: 94 [68,140] mg/dL; U-TNF: 60 [49, 84] mg/dL; p = 0.001). Serum TNF-α was not significantly different by group (VL: 6.3 [5.8, 7.0] pg/mL; ML: 6.1 [5.6, 6.5]; EC: 5.8 [5.3, 6.6]; p = 0.31), but was correlated with plasma TG (ρ = 0.40, p = 0.002). ConclusionsIn this exploratory cohort, TNF- α levels were higher in milk from mothers with low milk production, and both milk and serum TNF- α was associated with higher plasma TG. This suggests that proximal TNF-α expression is more associated with reduced mammary LpL activity than circulating serum TNF-α, leading to low milk production. Funding SourcesNIH and USDA.

Beyond Nutrient Deficiency-Opportunities to Improve Nutritional Status and Promote Health Modernizing DRIs and Supplementation Recommendations.

The US Dietary Guidelines for Americans (DGA) provide dietary recommendations to meet nutrient needs, promote health, and prevent disease. Despite 40 years of DGA, the prevalence of under-consumed nutrients continues in the US and globally, although dietary supplement use can help to fill shortfalls. Nutrient recommendations are based on Dietary Reference Intakes (DRIs) to meet the nutrient requirements for nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group and many need to be updated using current evidence. There is an opportunity to modernize vitamin and mineral intake recommendations based on biomarker or surrogate endpoint levels needed to ‘prevent deficiency’ with DRIs based on ranges of biomarker or surrogate endpoints levels that support normal cell/organ/tissue function in healthy individuals, and to establish DRIs for bioactive compounds. We recommend vitamin K and Mg DRIs be updated and DRIs be established for lutein and eicosapentaenoic and docosahexaenoic acid (EPA + DHA). With increasing interest in personalized (or precision) nutrition, we propose greater research investment in validating biomarkers and metabolic health measures and the development and use of inexpensive diagnostic devices. Data generated from such approaches will help elucidate optimal nutrient status, provide objective evaluations of an individual’s nutritional status, and serve to provide personalized nutrition guidance.

Cognitive ability and metabolic physical health in first-episode psychosis

Cognitive impairments are a core feature of first-episode psychosis (FEP), arising before illness onset and antipsychotic exposure. Individuals with chronic psychosis experience poorer physical health while taking antipsychotic medication, but health disparities may be evident at FEP onset, prior to antipsychotic exposure. Given the links between cognition and physical health in healthy populations, the aim was to explore whether cognition and physical health are associated in FEP, which could inform early physical health interventions for cognition in FEP. Participants were aged 15 to 25 and included 86 individuals experiencing FEP with limited antipsychotic exposure and duration of untreated psychosis of ≤six months, and 43 age- and sex-matched controls. Individuals with FEP performed significantly poorer than controls in most cognitive domains (Cohen's d = 0.38 to 1.59). Groups were similar in metabolic health measures, excluding a significantly faster heart rate in FEP (d = 0.68). Through hierarchical regression analyses, we found that in the overall sample, BMI was negatively related to current IQ after controlling for education and group (FEP/control). Relationships between BMI and cognition were consistent across the FEP and healthy control groups. In FEP, current IQ and working memory were negatively correlated with lipid profiles. Findings suggest that in FEP, impaired cognition is exhibited earlier than physical health problems, and that compared to controls, similar relationships with cognition are demonstrated. Causal pathways and trajectories of relationships between health and cognition in FEP require investigation, especially as antipsychotic medications are introduced. The findings have implications for cognitive and health interventions.

Reduced Olfactory Bulb Volume in Obesity and Its Relation to Metabolic Health Status.

Smell perception plays an important role in eating behavior and might be involved in body weight gain. Since a body of literature implies that olfactory perception and function is hampered in obesity, we here investigate neuroanatomical correlates of this phenomenon. We assessed olfactory bulb (OB) volume with magnetic resonance imaging in 67 healthy participants with a body mass index (BMI) from 18.9 to 45.4 kg/m2 (mean = 28.58 ± 6.64). Moreover, we obtained psychophysiological data on olfactory ability (Sniffin’ Sticks, Food associated odor test) and self-report measurements on eating behavior. Additionally, we collected parameters associated with metabolic health in obesity (waist-hip ratio, waist-height ratio, leptin levels, body fat percentage, fat mass index, insulin resistance) to investigate recently proposed mechanistic explanatory models of why olfaction may be altered in obesity. We showed that OB volume was significantly lower in participants with obesity when compared to those of normal weight. Moreover, we found weak to moderate negative correlations between OB volume and BMI and related measures of metabolic health, especially leptin, body fat percentage, waist-height ratio and insulin resistance. However, neither OB volume nor BMI were related to olfactory function in our young and healthy sample. Nevertheless, our results provide first indications that obesity is associated with brain anatomical changes in the OBs.

Comprehensive Metabolic Phenotyping Refines Cardiovascular Risk in Young Adults.

Whereas cardiovascular disease (CVD) metrics define risk in individuals >40 years of age, the earliest lesions of CVD appear well before this age. Despite the role of metabolism in CVD antecedents, studies in younger, biracial populations to define precise metabolic risk phenotypes are lacking. We studied 2330 White and Black young adults (mean age, 32 years; 45% Black) in the CARDIA study (Coronary Artery Risk Development in Young Adults) to identify metabolite profiles associated with an adverse CVD phenome (myocardial structure/function, fitness, vascular calcification), mechanisms, and outcomes over 2 decades. Statistical learning methods (elastic nets/principal components analysis) and Cox regression generated parsimonious, metabolite-based risk scores validated in >1800 individuals in the Framingham Heart Study. In the CARDIA study, metabolite profiles quantified in early adulthood were associated with subclinical CVD development over 20 years, specifying known and novel pathways of CVD (eg, transcriptional regulation, brain-derived neurotrophic factor, nitric oxide, renin-angiotensin). We found 2 multiparametric, metabolite-based scores linked independently to vascular and myocardial health, with metabolites included in each score specifying microbial metabolism, hepatic steatosis, oxidative stress, nitric oxide modulation, and collagen metabolism. The metabolite-based vascular scores were lower in men, and myocardial scores were lower in Black participants. Over a nearly 25-year median follow-up in CARDIA, the metabolite-based vascular score (hazard ratio, 0.68 per SD [95% CI, 0.50-0.92]; P=0.01) and myocardial score (hazard ratio, 0.60 per SD [95% CI, 0.45-0.80]; P=0.0005) in the third and fourth decades of life were associated with clinical CVD with a synergistic association with outcome (Pinteraction=0.009). We replicated these findings in 1898 individuals in the Framingham Heart Study over 2 decades, with a similar association with outcome (including interaction), reclassification, and discrimination. In the Framingham Heart Study, the metabolite scores exhibited an age interaction (P=0.0004 for a combined myocardial-vascular score with incident CVD), such that young adults with poorer metabolite-based health scores had highest hazard of future CVD. Metabolic signatures of myocardial and vascular health in young adulthood specify known/novel pathways of metabolic dysfunction relevant to CVD, associated with outcome in 2 independent cohorts. Efforts to include precision measures of metabolic health in risk stratification to interrupt CVD at its earliest stage are warranted.

A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health.

Animal data indicate that ketogenic diets are associated with improved mitochondrial function, but human data are lacking. We aimed to characterize skeletal muscle mitochondrial changes in response to a ketogenic diet combined with exercise training in healthy individuals. Twenty-nine physically active adults completed a 12-wk supervised exercise program after self-selection into a ketogenic diet (KD, n = 15) group or maintenance of their habitual mixed diet (MD, n = 14). Measures of metabolic health and muscle biopsies (vastus lateralis) were obtained before and after the intervention. Mitochondria were isolated from muscle and studied after exposure to carbohydrate (pyruvate), fat (palmitoyl-l-carnitine), and ketone (β-hydroxybutyrate+acetoacetate) substrates. Compared with MD, the KD resulted in increased whole body resting fat oxidation (P < 0.001) and decreased fasting insulin (P = 0.019), insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), P = 0.022], and visceral fat (P < 0.001). The KD altered mitochondrial function as evidenced by increases in mitochondrial respiratory control ratio (19%, P = 0.009), ATP production (36%, P = 0.028), and ATP/H2O2 (36%, P = 0.033) with the fat-based substrate. ATP production with the ketone-based substrate was four to eight times lower than with other substrates, indicating minimal oxidation. The KD resulted in a small decrease in muscle glycogen (14%, P = 0.035) and an increase in muscle triglyceride (81%, P = 0.006). These results expand our understanding of human adaptation to a ketogenic diet combined with exercise. In conjunction with weight loss, we observed altered skeletal muscle mitochondrial function and efficiency, an effect that may contribute to the therapeutic use of ketogenic diets in various clinical conditions, especially those associated with insulin resistance.

Facial appearance and metabolic health biomarkers in women

Facial appearance has been suggested to provide an honest cue of an individual’s biological condition. However, there is little direct evidence that facial attractiveness reflects actual health. Here we tested if facial appearance is related with metabolic health biomarkers. Face photographs of 161 healthy, young women (Mage = 28.59, SDage = 2.34) were assessed in terms of perceived attractiveness and health. Metabolic health was evaluated based on levels of markers of lipid and glucose metabolism balance, liver functioning, and inflammation. BMI, testosterone (T), and estradiol (E2) levels were controlled. Facial attractiveness, but not health, was negatively related with lipid profile components detrimental to health (total cholesterol, LDL, triglycerides) but not with relatively protective for health HDL. When controlled for BMI, E2, and T, only the relationship between attractiveness and triglycerides remained significant. Facial appearance was unrelated with glucose metabolism, liver functioning, and inflammatory markers. The results suggest, that for healthy women of reproductive age, such measures as BMI and sex hormone levels may be better predictors of attractiveness, compared to measures of metabolic health. Markers of lipid, glucose homeostasis, liver functioning or low-grade inflammation may be rather indicators of future health, of lesser importance in mating context, thus only modestly reflected in facial appearance.

Multi-Omic Biological Age Estimation and Its Correlation With Wellness and Disease Phenotypes: A Longitudinal Study of 3,558 Individuals.

Biological age (BA), derived from molecular and physiological measurements, has been proposed to better predict mortality and disease than chronological age (CA). In the present study, a computed estimate of BA was investigated longitudinally in 3,558 individuals using deep phenotyping, which encompassed a broad range of biological processes. The Klemera-Doubal algorithm was applied to longitudinal data consisting of genetic, clinical laboratory, metabolomic, and proteomic assays from individuals undergoing a wellness program. BA was elevated relative to CA in the presence of chronic diseases. We observed a significantly lower rate of change than the expected ~1 year/year (to which the estimation algorithm was constrained) in BA for individuals participating in a wellness program. This observation suggests that BA is modifiable and suggests that a lower BA relative to CA may be a sign of healthy aging. Measures of metabolic health, inflammation, and toxin bioaccumulation were strong predictors of BA. BA estimation from deep phenotyping was seen to change in the direction expected for both positive and negative health conditions. We believe BA represents a general and interpretable "metric for wellness" that may aid in monitoring aging over time.

MULTI-OMIC BIOLOGICAL AGE ESTIMATION, CORRELATION WITH WELLNESS, DISEASE PHENOTYPES: LONGITUDINAL SAMPLE OF 3558

Biological age (BA) has been shown to be a better predictor of mortality and disease than chronological age (CA). Aging’s diverse effects are visible across many data types. We investigated BA from deep phenotyping of 3558 wellness program participants and controls. The Klemera-Doubal BA estimation algorithm was applied to genetic and longitudinal clinical laboratory, metabolomic, and proteomic assay data. BA trajectories were calculated using Generalized Estimating Equations. BA of individuals with Type-2 Diabetes averaged 6+ years greater than CA. Wellness program participation decreased individuals’ rate of aging (coefficient: -0.16, 95% CI: -0.45, 0.19), with effects dependent on sex, initial BA, and CA. Measures of metabolic health, inflammation, and toxin bioaccumulation were strong predictors across data types and sex. Deep phenotyping enabled calculation of a BA measure and a wellness program improved BA, either in absolute terms or relative to CA, showing it is modifiable.

Quantitative assessment of betainized compounds and associations with dietary and metabolic biomarkers in the randomized study of the healthy Nordic diet (SYSDIET)

Recently, a group of betainized compounds have been suggested to play a role in health effects in relation to a whole-grain-rich diet. The aims of this study were to develop a quantitative mass spectrometric method for selected betainized compounds in human plasma, and to investigate their association with nutrient intake and measures of metabolic health in participants of the SYSDIET study. The SYSDIET study was a controlled randomized intervention including individuals with metabolic syndrome, where the healthy Nordic diet (HND) group increased intakes of whole grains, canola oil, berries, and fish, whereas the control diet (CD) group consumed low-fiber cereal products, milk fat, and restricted amounts of fish and berries. A quantitative LC combined with triple quadrupole MS method for betainized compounds was developed and applied to fasting plasma samples from baseline (week 0) and the end of the intervention (week 18 or 24). Concentrations of betainized compounds were correlated with intakes of selected nutrients and fiber and measures of metabolic health. Pipecolic acid betaine (PAB) concentrations were significantly higher in the HND group than in the CD group (P=0.00032) at the end of the intervention and correlated directly (P<0.0001) with intakes of dietary fiber (r=0.376) and a biomarker related to whole-grain rye intake, namely the ratio of alkylresorcinol C17:0 to C21:0 (r=0.442). PAB was associated inversely with fasting plasma insulin consistently at the beginning and at the end of the intervention (P<0.001, r=-0.300; P<0.01, r=-0.250, respectively), as well as IL-1 receptor antagonist (P<0.01, r=-0.232 at the beginning; P<0.01, r=-0.236 at the end) and serum LDL/HDL cholesterol (P<0.01, r=-0.239 at the beginning; P<0.01, r=-0.241 at the end). Among adults with the metabolic syndrome, PAB plasma concentrations were associated with fasting insulin, inflammation, and lipids and were significantly increased with adoption of the HND. Further studies are needed to clarify the biological functions of betainized compounds. This trial was registered at clinicaltrials.gov as NCT00992641.

Beneficial effect of personalized lifestyle advice compared to generic advice on wellbeing among Dutch seniors – An explorative study

The aim of this explorative study is to evaluate whether personalized compared to generic lifestyle advice improves wellbeing in a senior population. We conducted a nine-week single-blind randomized controlled trial including 59 participants (age 67.7 ± 4.8 years) from Wageningen and its surrounding areas in the Netherlands. Three times during the intervention period, participants received either personalized advice (PA), or generic advice (GA) to improve lifestyle behavior. Personalization was based on metabolic health measures and dietary intake resulting in an advice that highlighted food groups and physical activity types for which behavior change was most urgent. Before and after the intervention period self-perceived health was evaluated as parameter of wellbeing using a self-perceived health score (single-item) and two questionnaires (Vita-16 and Short Form-12). Additionally, anthropometry and physical functioning (short physical performance battery, SPPB) were assessed.Overall scores for self-perceived health did not change over time in any group. Resilience and motivation (Vita-16) slightly improved only in the PA group, whilst mental health (SF-12) and energy (Vita-16) showed slight improvement only in the GA group. SPPB scores improved over time in both the PA and GA group. PA participants also showed a reduction in body fat percentage and hip circumference, whereas these parameters increased in the GA group Our findings suggest that although no clear effects on wellbeing were found, still, at least on the short term, personalized advice may evoke health benefits in a population of seniors as compared to generic advice.

OR31-2 Effects of Colchicine on Insulin Resistance, Pancreatic Beta-Cell Function, and Aspects of the Metabolic Syndrome (MetS) in Adults with Obesity, MetS, and Inflammation: A Pilot Randomized Controlled Trial

Introduction: Low-grade chronic inflammation, due in part to activation of the NLRP3 inflammasome, increases with increasing adiposity and plays a significant role in the development of type 2 diabetes and cardiovascular disease. However, to date, the efficacy of anti-inflammatory medications to improve aspects of the metabolic syndrome (MetS) is not well established. As colchicine has been shown to prevent assembly of the NLRP3 inflammasome and ameliorate other inflammatory conditions, we aimed to evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in adults with obesity and MetS. Materials and Methods: We conducted a randomized, double-blind, placebo-controlled pilot trial in which 40 non-diabetic adults with obesity, MetS, and elevated high-sensitivity C-reactive protein (hsCRP≥ 2.0 mg/L) were randomized to colchicine 0.6 mg or placebo twice daily for three months. Fasting labs, insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT), and body composition by DXA were performed at baseline and 3-month follow up. The primary outcome was change in FSIVGTT insulin sensitivity (SI) as measured by Bergman’s minimal model. Secondary outcomes included changes in other metabolic parameters and inflammatory markers. ANCOVA was used to examine differences between treatment arms, with age, sex, baseline body fat%, and Δbody fat% as covariates. Data were analyzed according to intention-to-treat and reported as mean±SD. Results: Colchicine significantly reduced inflammatory indices, including hsCRP (-2.8±2.9 vs. 0.4±2.8 mg/L, p=.002), ESR (-5.5±6.4 vs. 0.6±6.3 mm/hr, p=.007), white blood cell count (-1.09±1.23 vs. 0.29±1.16 K/µL, p=.002), and absolute neutrophil count (-1.06±1.05 vs. 0.12±0.93 K/µL, p<.001). However, change in SI was not significantly different between colchicine and placebo arms (2.9x10-6 ± 3.1x10-5 vs 3.4x10-6 ± 2.9x10-5 min-1·mU-1·ml, p=.82). Changes in other metabolic parameters also did not reach significance, although changes in HOMA-IR (p=.097) and glucose effectiveness (SG; p=.067) trended towards improvement in the colchicine group. Adverse events were similar in both groups, and no patients withdrew due to side effects. Post-hoc analyses calculated that a sample size of 166 subjects would be necessary to achieve 80% power to detect a difference in measures of metabolic health (e.g. HOMA-IR, fasting insulin, fasting glucose, SG, and disposition index) between colchicine and placebo groups, for a two-tailed α <0.05. Conclusions: Colchicine significantly improved obesity-associated inflammatory variables and demonstrated a good safety profile among obese non-diabetic adults with MetS. Larger, adequately powered studies are needed to determine whether colchicine has beneficial effects on insulin resistance and other measures of metabolic health in at-risk individuals.

The Gut Microbiome on a Periodized Low-Protein Diet Is Associated With Improved Metabolic Health.

A periodized (14 days on/14 days off) 5% low protein-high carbohydrate (pLPHC) diet protects against weight gain, improves glucose tolerance in mice and interacts with concurrent voluntary activity wheel training on several parameters including weight maintenance and liver FGF21 secretion. The gut microbiome (GM) responds to both diet and exercise and may influence host metabolism. This study compared the cecal GM after a 13.5-week intervention study in mice on a variety of dietary interventions ± concurrent voluntary exercise training in activity wheels. The diets included chronic chow diet, LPHC diet, 40 E% high protein-low carbohydrate (HPLC) diet, an obesigenic chronic high-fat diet (HFD) and the pLPHC diet. Our hypothesis was that the GM changes with pLPHC diet would generally reflect the improved metabolic health of the host and interact with concurrent exercise training. The GM analyses revealed greater abundance phylum Bacteroidetes and the genus Akkermansia on chronic and periodized LPHC and higher abundance of Oscillospira and Oscillibacter on HFD. The differences in diet-induced GM correlated strongly with the differences in a range of host metabolic health-measures. In contrast, no significant effect of concurrent exercise training was observed. In conclusion, pLPHC diet elicits substantial changes in the GM. In contrast, only subtle and non-significant effects of concurrent activity wheel exercise were observed. The pLPHC-associated microbiome may contribute to the healthier host phenotype observed in these mice.

Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial.

To evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS). Adults with obesity and MetS, but who did not have diabetes, were randomized to colchicine 0.6 mg or placebo capsules twice daily for 3 months. The primary outcome was change in insulin sensitivity (SI ) as estimated by insulin-modified frequently sampled intravenous glucose tolerance tests. Secondary outcomes included changes in other metabolic variables and inflammatory markers. Of 40 participants randomized (21 colchicine, 19 placebo), 37 completed the trial. Compared with placebo, colchicine significantly reduced C-reactive protein (P <0.005), erythrocyte sedimentation rate (P <0.01), white blood cell count (P <0.005), and absolute neutrophil count (P <0.001). Change in SI was not significantly different between colchicine and placebo arms (difference: +0.21 × 10-5 ; CI -1.70 to +2.13 × 10-5 min-1 mU-1 mL; P = 0.82). However, changes in some secondary outcomes, including homeostatic model assessment of insulin resistance (P = 0.0499), fasting insulin (P = 0.07) and glucose effectiveness (P = 0.08), suggested metabolic improvements in the colchicine versus placebo group. Adverse events were generally mild and similar in both groups. This pilot study found colchicine significantly improved obesity-associated inflammatory variables and showed a good safety profile among adults with obesity and MetS who did not have diabetes. These results suggest a larger, adequately powered study should be conducted to determine whether colchicine improves insulin resistance and other measures of metabolic health in at-risk individuals.

Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial.

BackgroundLow-carbohydrate, high-fat (LCHF) diets are useful for treating a range of health conditions, but there is little research evaluating the degree of carbohydrate restriction on outcome measures. This study compares anthropometric and cardiometabolic outcomes between differing carbohydrate-restricted diets.ObjectiveOur hypothesis was that moderate carbohydrate restriction is easier to maintain and more effective for improving cardiometabolic health markers than greater restriction.DesignA total of 77 healthy participants were randomised to a very low-carbohydrate ketogenic diet (VLCKD), low-carbohydrate diet (LCD), or moderate-low carbohydrate diet (MCD), containing 5%, 15% and 25% total energy from carbohydrate, respectively, for 12-weeks. Anthropometric and metabolic health measures were taken at baseline and at 12 weeks. Using ANOVA, both within and between-group outcomes were analysed.ResultsOf 77 participants, 39 (51%) completed the study. In these completers overall, significant reductions in weight and body mass index occurred ((mean change) 3.7 kg/m2; 95% confidence limits (CL): 3.8, 1.8), along with increases in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, (0.49 mmol/L; 95% CL; 0.06, 0.92; p = 0.03), and total cholesterol concentrations (0.11 mmol/L; 95% CL; 0.00, 0.23; p = 0.05). Triglyceride (TG) levels were reduced by 0.12 mmol/L (95% CL; −0.20, 0.02; p = 0.02). No significant changes occurred between groups. The largest improvements in high density lipoprotein cholesterol (HDL-c) and TG and anthropometric changes occurred for the VLCKD group.ConclusionsLow-carbohydrate, high-fat diets have a positive effect on markers of health. Adherence to the allocation of carbohydrate was more easily achieved in MCD, and LCD groups compared to VLCKD and there were comparable improvements in weight loss and waist circumference and greater improvements in HDL-c and TG with greater carbohydrate restriction.

38. Relationship between early pregnancy nutrition and abdominal subcutaneous fat

Introduction Objective clinical measures of metabolic health during pregnancy would be desirable. As recent work suggests dietary macronutrient balance is important in regulating energy intake and metabolic health the aim of this study was to assess the associations between dietary macronutrient composition and US measures of SAT layers. Method 200 women recruited at 11–14 weeks gestation completed a food frequency questionnaire and measurements were performed on abdominal SAT, dividing it into the two anatomical layers superficial SAT (SSAT) and deep SAT (DSAT), assessing SAT density with US strain elastography. Plausible diets of 185 women were used. Generalised additive models using thin plate regression splines were used to associate intake of dietary protein, carbohydrate and fat (kJ/day) with these measures of SAT. Result Dietary intake did not differ between the body mass index (BMI) categories, except when macronutrients intakes were adjusted for weight. In early pregnancy, there was an association between a high protein, low fat intake diet with increased SSAT thickness. There was no significant association of macronutrient intake with DSAT. When assessing the relationship of SAT density with macronutrient intake there was an association between decreased density of SSAT with low fat intake. There was no association of macronutrients and SAT density in the DSAT. Conclusion Although it is difficult to make assumptions from human studies using dietary recollection and considering a life-time of dietary pattern has contributed to the current body AT, macronutrient balance may have a prominent place in metabolic health, deposition and density of AT and long-term AT distribution. Prospective studies are warranted to investigate whether SAT measures meaningfully reflect macronutrient composition and metabolic health in pregnancy.

The effects of increased hay‐to‐grain ratio on behavior, metabolic health measures, and fecal bacterial communities in four Masai giraffe (Giraffa camelopardalis tippelskirchi) at Cleveland Metroparks Zoo

We evaluated whether increasing the hay-to-grain ratio offered to Masai giraffe (Giraffa camelopardalis tippelskirchi) at Cleveland Metroparks Zoo would reduce oral stereotypies and alter feeding behaviors, maintain or increase serum calcium-to-phosphorus ratio, decrease serum insulin-to-glucose ratio and salivary insulin, and alter fecal bacterial community structure. Giraffe transitioned to a ∼90:10 hay-to-grain ratio in even increments over 8 weeks. A ration balancer was added during the seventh week of transition to ensure proper mineral and nutrient balance. We collected (1) behavioral data collected approximately daily using instantaneous focal sampling; (2) serum collections every other week for insulin-to-glucose and calcium-to-phosphorus ratio analysis and saliva weekly for insulin analysis; and (3) weekly fecal sample collections to examine changes in bacterial community structure during the 8 weeks preceding and following the diet change. After the diet change, giraffe spent significantly more time feeding and less time performing tongue and mouth stereotypies, people-directed and alert behaviors. Salivary and serum insulin and serum insulin-to-glucose ratio decreased, and fecal bacterial community structure changed significantly. However, serum calcium-to-phosphorus ratio remained >1:1 throughout the study. While further studies are needed to elucidate the nature and implications of the change in fecal bacterial community structure and metabolic hormones, the results of this study show promise for incremental improvements in health and welfare from feeding a higher proportion of forage in the diet.

Metabolic Syndrome and Prediabetes Fail to Detect a High Prevalence of Early Insulin Resistance—The PREMIER Study

The PREMIER Study was a multi-center randomized controlled trial of lifestyle interventions in 810 nondiabetic subjects with elevated blood pressure. At baseline, one half of the cohort met the criteria for metabolic syndrome (MetS) and one third met the fasting glucose criterion for prediabetes (PreD). The purpose of the current analysis of PREMIER data was to quantify the sensitivity of the MetS criteria and cut points for detecting hyperinsulinemia and insulin resistance, defined here as fasting insulin ≥ 12 μIU/mL based on prior calibration against the euglycemic clamp. Insulin showed statistically significant bivariate correlations with 4 of the 5 MetS criteria in decreasing order of strength: waist circumference, fasting glucose, HDL-cholesterol and fasting triglycerides. By contrast, systolic and diastolic blood pressure, and total- and LDL-cholesterol did not correlate with fasting insulin. Logistic regression revealed that each MetS criterion, except blood pressure, had an independent contribution to hyperinsulinemia, even after correcting for age, race and gender. Receiver operator characteristic curves showed that the harmonized MetS cut points were non-optimal for detecting hyperinsulinemia. Specifically, the fasting triglyceride and glucose cut points were too high, while those for waist circumference were too low. Using the criteria for MetS and hyperinsulinemia, the subjects were divided into four metabolic subtypes. The subtype with hyperinsulinemia but not MetS represented 14.7% (95% CI 12.4-17.5) of the cohort. The prevalence of individuals with hyperinsulinemia that did not meet the criteria for MetS or PreD was surprisingly high at 12.7% (95% CI 10.3-15.1). This subtype is an important target for early intervention and diabetes prevention, but was not detected in this population using the current criteria for MetS or PreD. New screening strategies and metabolic health measures are needed to improve outcomes for diabetes prevention. Disclosure D.P. Cistola: None. A.K. Dwivedi: None. J.D. Ard: Consultant; Self; Nestlé. Research Support; Self; Nestlé, VIVUS, Inc..

Identifying poor metabolic adaptation during early lactation in dairy cows using cluster analysis

Currently, cows with poor metabolic adaptation during early lactation, or poor metabolic adaptation syndrome (PMAS), are often identified based on detection of hyperketonemia. Unfortunately, elevated blood ketones do not manifest consistently with indications of PMAS. Expected indicators of PMAS include elevated liver enzymes and bilirubin, decreased rumen fill, reduced rumen contractions, and a decrease in milk production. Cows with PMAS typically are higher producing, older cows that are earlier in lactation and have greater body condition score at the start of lactation. It was our aim to evaluate commonly used measures of metabolic health (input variables) that were available [i.e., blood β-hydroxybutyrate acid, milk fat:protein ratio, blood nonesterified fatty acids (NEFA)] to characterize PMAS. Bavarian farms (n = 26) with robotic milking systems were enrolled for weekly visits for an average of 6.7 wk. Physical examinations of the cows (5-50 d in milk) were performed by veterinarians during each visit, and blood and milk samples were collected. Resulting data included 790 observations from 312 cows (309 Simmental, 1 Red Holstein, 2 Holstein). Principal component analysis was conducted on the 3 input variables, followed by K-means cluster analysis of the first 2 orthogonal components. The 5 resulting clusters were then ascribed to low, intermediate, or high PMAS classes based on their degree of agreement with expected PMAS indicators and characteristics in comparison with other clusters. Results revealed that PMAS classes were most significantly associated with blood NEFA levels. Next, we evaluated NEFA values that classify observations into appropriate PMAS classes in this data set, which we called separation values. Our resulting NEFA separation values [<0.39 mmol/L (95% confidence limits = 0.360-0.410) to identify low PMAS observations and ≥0.7 mmol/L (95% confidence limits = 0.650-0.775) to identify high PMAS observations] were similar to values determined for Holsteins in conventional milking settings diagnosed with hyperketonemia and clinical symptoms such as anorexia and a reduction in milk yield, as reported in the literature. Future studies evaluating additional clinical and laboratory data, breeds, and milking systems are needed to validate these finding. The aim of future studies would be to build a PMAS prediction model to alert producers of cows needing attention and help evaluate on-farm metabolic health management at the herd level.

A Role for DPP4 Expression via Oxidized LDL/TLR4/TRIF/CD36 Pathways in Human Obesity and Atherosclerosis

Abstract Objective Dipeptidyl peptidase IV (DPP4) is well-known for its regulatory role in incretin biology. Although prior studies have suggested a role for DPP4 in atherosclerosis, the regulation of DPP4 in diabetes and atherosclerosis has not been investigated. In this study, we investigated the relationship of DPP4 with human aortic atherosclerosis and the role of obesity. Methods and Results We tested the expression of membrane bound DPP4 on circulating monocytes and plasma DPP4 activity (cleaved) in patients with atherosclerosis and their relationship with measures of metabolic health. In atherosclerosis, both cleaved and membrane bound DPP4 were increased. DPP4 expression on monocytes was positively correlated with atherosclerotic plaque volume assessed by high-resolution MRI with expression positively correlating with non-HDL cholesterol level (P=0.0242) but not fasting blood glucose or insulin. Oxidized low-density lipoprotein (oxLDL) up-regulated DPP4 expression on macrophages with a preferential increase in CD36+ cells. OxLDL mediated increase in DPP4 was abolished by siRNA-mediated Toll-like receptor 4 (TLR4) knock-down and considerably diminished by CD36 deficiency. Loss of TRIF but not MyD88 attenuated DPP4 increase with oxLDL. Conclusions DPP4 expression on monocytes correlates with atherosclerotic plaque volume with a key role for oxidized LDL in regulating DPP4 expression via CD36/TLR4/TRIF pathways. Increased DPP4 in response to oxidized lipids may represent an integrated mechanism by which post-prandial glucose metabolism is linked to lipoprotein abnormalities potentiates atherosclerosis.