Changes In Respiratory Quotient Research Articles

The Energetic Saver Profile From Sit-to-Stand Does Not Persist During Very Low-Intensity Physical Activity in Healthy Men and Women.

It is essential to better characterize the energetic profile of individuals during very low-intensity physical activity. The objectives of the present study were to determine whether the saver profile from sit-to-stand persists during light physical activity and characterize patterns in substrate utilization from sit-to-stand and during very low-intensity physical activity in healthy men and women. Sixty-two healthy adults (38 women) performed an experimental sequence that corresponded to 15-minute sitting (SIT1), followed by 15-minute standing (STAND), 15-minute sitting again (SIT2), and finally 15minutes of light cycling. Continuous indirect calorimetry was allowed to calculate energy expenditure (EE) and respiratory quotient through the entire sequence. Savers and nonsavers (<5% and ≥ 5% increase in EE from sitting to standing, respectively) were determined. There was an interaction effect in EE between savers and nonsavers through the whole sequence (P = .008). Only nonsavers (71%) exhibited a significant increase in EE from SIT1 to STAND (P < .001). Nonsavers and savers significantly increased EE during 15minutes of light cycling relative to sitting or standing (P < .001), without any difference between groups. The percentage of change in respiratory quotient from SIT1 to STAND was significantly different between the 2 groups, with increased values in savers and decreased values in nonsavers (P = .03). Significantly lower values in respiratory quotient and EE were found during 15minutes of light cycling in women compared with men (P < .001). It is essential to determine individuals' energetic phenotype to determine those who may benefit more from strategies such as standing or light physical activity. The sexual dimorphism in terms of substrate use during such exercise should be considered.

Assessing metabolic flexibility response to a multifibre diet: a randomised-controlled trial.

Metabolic flexibility (MetF), defined as the ability to switch between fat and glucose oxidation, is increasingly recognised as a critical marker for assessing responses to dietary interventions. Previously, we showed that the consumption of multifibre bread improved insulin sensitivity and reduced low-density lipoprotein cholesterol (LDLc) levels in overweight and obese individuals. As a secondary objective, we aimed to explore whether our intervention could also improve MetF. In this study, 39 subjects at cardiometabolic risk participated in a double-blind, randomised, crossover trial lasting 8 weeks, repeated twice. During each phase, participants consumed either 150 g of standard bread daily or bread enriched with a mixture of seven dietary fibres. MetF response was assessed using a mixed-meal tolerance test (MMTT), analysing changes in respiratory quotient (∆RQ) measured using indirect calorimetry. Although there were no significant differences in ∆RQ changes induced by dietary fibre between the two diets, these changes were positively correlated with postprandial triglyceride excursion (∆TG) at baseline. Subgroup analysis of baseline fasting and postprandial plasma metabolites was conducted to characterise MetF responders. These responders exhibited higher baseline fasting LDLc levels and greater post-MMTT ∆TG. In conclusion, although dietary fibres did not directly impact MetF in this study, our findings highlight potential determinants of MetF response, warranting further investigation in dedicated future interventions.

Effect of carnitine supplementation on energy utilization in patients with type 2 diabetes and long-term tube feeding: A CARE-compliant case report

Introduction: Carnitine is essential for the energy utilization of long-chain fatty acids. However, the effects of carnitine supplementation on patients undergoing tube feeding remain unclear, and some enteral formula products do not contain carnitine. In order to gain insights into the role of carnitine supplementation on energy utilization in patients with long-term tube feeding, we observed the changes in respiratory quotient (RQ) of patients before and after the addition of carnitine due to the renewal of an enteral formula product. Case presentation: We observed 6 patients who continued tube feeding with the same enteral formula product scheduled for renewal. All 6 participants had diabetes, and indirect calorimetry data were available for 4 patients. Participants were observed for 3 months after switching to the new formulation. After the switching, a carnitine supplementation of 120 to 180 mg/day was provided, depending on the intake amount. One month after switching, blood free carnitine and total carnitine levels in all 6 patients increased from below the lower limit to within the range of the Japanese reference standard. In 3 of the 4 patients for whom indirect calorimetry was possible, the fasting RQ at baseline was &gt;0.90, suggesting impaired lipid utilization. The mean fasting RQ significantly decreased 2 months after the switch. The 1- and 2-hour postprandial RQ also showed a significant decrease after switching. Conclusion: Carnitine supplementation of enteral formulas may be important for normal energy utilization of lipids in patients receiving long-term tube feeding. An evaluation using randomized controlled trials with a larger number of patients is required.

Substrate metabolism in male astronauts onboard the International Space Station: the ENERGY study

Bedrest shifts fasting and postprandial fuel selection towards carbohydrate use over lipids, potentially affecting astronauts’ performance and health. We investigated whether this change occurs in astronauts after at least 3 months onboard the International Space Station (ISS). We further explored the associations with diet, physical activity (PA), and body composition. Before and during spaceflight, respiratory quotient (RQ), carbohydrate, and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 males (age = 45.7 [SD 7.7] years, BMI = 24.3 [2.1] kg m−²). Postprandial substrate use was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). Food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and PA by accelerometry and diary logs. Spaceflight increased fasting RQ (P = 0.01) and carbohydrate oxidation (P = 0.04) and decreased fasting lipid oxidation (P < 0.01). An increase in FQ (P < 0.001) indicated dietary modifications onboard the ISS. Spaceflight-induced RQ changes adjusted for ground RQ correlated with inflight FQ (P < 0.01). In postprandial conditions, nutrient oxidation and ΔRQ were unaffected on average. Lipid oxidation changes negatively correlated with FFM changes and inflight aerobic exercise and positively with FM changes. The opposite was observed for carbohydrate oxidation. ΔRQ changes were negatively and positively related to FM and FFM changes, respectively. In conclusion, fasting substrate oxidation shift observed during spaceflight may primarily result from dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight PA.

Based on P (cv-a) CO2/C (a-cv) O2 and its changes are associated with an early reduction in multiple organ failure in patients with septic hyperlactocidemia

ABSTRACT The study aimed to investigate the relationship between the respiratory quotient (RQ), measured by the central venous-arterial carbon dioxide partial pressure difference/arterial-venous oxygenation difference ratio, and the early remission of multi-organ failure (MOF) in sepsis patients with hyperlactatemia. The study observed 49 septic patients with hyperlactatemia in the ICU, obtaining blood samples before and after resuscitation, and dividing the patients into two groups depending on whether the modified Sequential Organ Failure Assessment score improved after 24 hours of treatment. Results showed that lactate clearance was faster and the rate of change in RQ was higher in the improved group than in the unimproved group. Further analysis showed that an RQ ≤0.198 mmHg/mL/L or a change of ≥30.71% in RQ after 24 hours of resuscitation was associated with early improvement in MOF. In conclusion, changes in RQ were associated with early improvement in MOF in septic patients with hyperlactatemia, suggesting that RQ could be used as a potential marker for predicting early remission and guiding clinical interventions.

Introduction of adult cats to indirect calorimetry respiration chambers causes increased energy expenditure and respiratory quotient that decrease following acclimation.

To replicate a previously defined behavioral procedure to acclimate adult cats to temporary restriction in indirect calorimetry chambers and measure energy expenditure and respiratory quotient changes during acclimation. 8 healthy adult cats (4 spayed females, and 4 neutered males; mean ± SEM age, 2.5 ± 1.5 years; mean body weight, 4.8 ± 1.8 kg). Cats underwent a 13-week incremental acclimation procedure whereby cats were acclimated to the chambers in their home environment (weeks 1 to 3), to the study room (weeks 4 to 6), and to increasing lengths of restriction within their home environment (weeks 7 to 8) and the chambers (weeks 9 to 13). Cat stress score, respiratory rate, fearfulness (assessed with a novel object test), energy expenditure, and respiratory quotient were measured. Data were analyzed by use of a repeated-measures mixed model. Stress, based on cat stress scores, fearfulness, and respiration, peaked at weeks 4, 9, and 10 but returned to baseline levels by week 11. Energy expenditure and respiratory quotient peaked at weeks 10 and 11, respectively, but were reduced significantly by weeks 11 and 13, respectively. All cats returned to baseline by the end of the study and were deemed fully acclimated. Changes in perceived stress level, energy expenditure, and respiratory quotient at various stages of the acclimation procedure suggest that stress should be considered a significant variable in energy balance measurements when indirect calorimetry is used in cats. An incremental acclimation procedure should therefore be used to prepare cats for the temporary space restriction necessary for indirect calorimetry studies.

Similar Metabolic Health in Overweight/Obese Individuals With Contrasting Metabolic Flexibility to an Oral Glucose Tolerance Test.

Background: Low metabolic flexibility (MetF) may be an underlying factor for metabolic health impairment. Individuals with low MetF are thus expected to have worse metabolic health than subjects with high MetF. Therefore, we aimed to compare metabolic health in individuals with contrasting MetF to an oral glucose tolerance test (OGTT).Methods: In individuals with excess body weight, we measured MetF as the change in respiratory quotient (RQ) from fasting to 1 h after ingestion of a 75-g glucose load (i.e., OGTT). Individuals were then grouped into low and high MetF (Low-MetF n = 12; High-MetF n = 13). The groups had similar body mass index, body fat, sex, age, and maximum oxygen uptake. Metabolic health markers (clinical markers, insulin sensitivity/resistance, abdominal fat, and intrahepatic fat) were compared between groups.Results: Fasting glucose, triglycerides (TG), and high-density lipoprotein (HDL) were similar between groups. So were insulin sensitivity/resistance, visceral, and intrahepatic fat. Nevertheless, High-MetF individuals had higher diastolic blood pressure, a larger drop in TG concentration during the OGTT, and a borderline significant (P = 0.05) higher Subcutaneous Adipose Tissue (SAT). Further, compared to Low-MetF, High-MetF individuals had an about 2-fold steeper slope for the relationship between SAT and fat mass index.Conclusion: Individuals with contrasting MetF to an OGTT had similar metabolic health. Yet High-MetF appears related to enhanced circulating TG clearance and enlarged subcutaneous fat.

Respiratory Quotient Is Correlated With Reductions In Aerobic Exercise Performance Following Repeated 6-hour Hyperoxic Dives

Hyperoxic conditions can lead to decrements in performance following repeated long-duration 100% O2 dives, but mechanisms for reductions in exercise capacity are not well understood. PURPOSE: Measure respiratory quotient (RQ) and related metabolic variables to identify factors contributing to aerobic performance decrements post-dive. METHODS: 14 military divers completed 5 consecutive 6-hr 100% O2 exercise dives at 1.35 ATA with 18-hr surface intervals. A time-to-fatigue treadmill run at 85% of maximal O2 consumptions (V̇O2max) was completed 72 hrs before dive 1 (PRE), within 2 hrs after dive 5 (2POST), and at 72 hrs after dive 5 (72POST). Breath-by-breath measures of RQ, V̇O2, and PetCO2 were taken during the runs; rating of perceived exertion (RPE) and breathing frequency (BF) were also measured. Data were time-matched to the end-point of the shortest run and analyzed using a one-way repeated measures ANOVA at PRE, 2POST, and 72POST. RESULTS: There were significant main effects for run time, RQ, Pet-CO2, V̇O2, BF, and RPE (p < 0.05). Run time significantly decreased from PRE (8.4 ± 0.8 min, mean ± SEM) to 2POST (4.6 ± 0.4 min, p < 0.01), and 72POST (6.3 ± 0.7 min, p < 0.01). RQ significantly increased from PRE (1.20 ± 0.01) to 2POST (1.25 ± 0.02, p < 0.01), but was not different at 72POST (1.21 ± 0.01). Change in RQ from PRE to 2POST and 72POST was highly correlated with endurance run time (r = -0.74, p < 0.01; r = -0.87, p < 0.01). PetCO2was lower than PRE (5.8 ± 0.2%) at 2POST (5.4 ± 0.2%, p < 0.01) and 72POST (5.4 ± 0.2%, p < 0.01), while V̇O2 was lower than PRE (3.5 ± 0.2 L/min) at 72POST only (3.2 ± 0.2 L/min, p < 0.01). BF was higher than PRE (39.2 ± 2.0 breaths/min) at 2POST (41.4 ± 2.0 breaths/min, p < 0.05) only. RPE was higher at both 2POST (16.4 ± 0.9, p < 0.01) and 72POST (15.5 ± 0.7, p < 0.05) compared to PRE (14.4 ± 1.0). CONCLUSION: The increase in RQ at 2POST suggests greater reliance on anaerobic glycolysis for energy following repetitive, long-duration 100% O2 dives. Correlation between RQ and run time suggests that failure to maintain oxidative phosphorylation may be a mechanism for decrements in performance. Future studies will investigate the effects of this type of diving on mitochondrial function and damage, which may be related to changes in RQ. Supported by the Office of Naval Research and NAVSEA Deep Submergence Biomedical Development Program

Effect of Dietary Strategies on Respiratory Quotient and Its Association with Clinical Parameters and Organ Fat Loss: A Randomized Controlled Trial.

The relation between changes in respiratory quotient (RQ) following dietary interventions and clinical parameters and body fat pools remains unknown. In this randomized controlled trial, participants with moderate abdominal obesity or/and dyslipidemia (n = 159) were randomly assigned to a Mediterranean/low carbohydrate (MED/LC, n = 80) or a low fat (LF, n = 79) isocaloric weight loss diet and completed a metabolic assessment. Changes in RQ (measured by indirect calorimeter), adipose-tissue pools (MRI), and clinical measurements were assessed at baseline and after 6 months of intervention. An elevated RQ at baseline was significantly associated with increased visceral adipose tissue, hepatic fat, higher levels of insulin and homeostatic insulin resistance. After 6 months, body weight had decreased similarly between the diet groups (−6 ± 6 kg). However, the MED/LC diet, which greatly improved metabolic health, decreased RQ significantly more than the LF diet (−0.022 ± 0.007 vs. −0.002 ± 0.008, p = 0.005). Total cholesterol and diastolic blood pressure were independently associated with RQ changes (p = 0.045). RQ was positively associated with increased superficial subcutaneous-adipose-tissue but decreased renal sinus, pancreatic, and intramuscular fats after adjusting for confounders. Fasting RQ may reflect differences in metabolic characteristics between subjects affecting their potential individual response to the diet.

Key Role of Respiratory Quotient to Reduce the Occurrence of Hypoxemia During Extracorporeal Gas Exchange: A Theoretical Analysis.

Extracorporeal respiratory support, including low blood flow systems providing mainly extracorporeal CO2 removal, are increasingly applied in clinical practice. Gas exchange physiology during extracorporeal respiratory support is complex and differs between full extracorporeal membrane oxygenation and extracorporeal CO2 removal. Aim of the present article is to review pathophysiological aspects which are relevant for the understanding of hypoxemia development during extracorporeal CO2 removal. We will describe the mathematical and physiologic background underlying changes in respiratory quotient and alveolar oxygen tension during venovenous extracorporeal gas exchange and highlight the clinical implications. Theoretical analysis of venovenous extracorporeal gas exchange. Italian university research hospital. None. None. While the effect of extracorporeal CO2 removal on the respiratory quotient of the native lung has long been known, the role of extracorporeal oxygenation in dictating changes in the respiratory quotient has been less addressed. Indeed, both extracorporeal CO2 removal and extracorporeal oxygen delivery affect the respiratory quotient of the native lung and thus influence the alveolar PO2. Indeed, for the same amount of extracorporeal CO2 extraction, it is possible to reduce the FIO2, reduce the risk of absorption atelectasis, and maintain the same alveolar PO2, by increasing the extracorporeal oxygen delivery. Worsening of hypoxemia is frequent during low-flow extracorporeal CO2 removal combined with ultraprotective mechanical ventilation. In this context, increasing extracorporeal oxygen delivery, increases the respiratory quotient of the native lung and could reduce both the occurrence of alveolar hypoxia and absorption atelectasis, thus optimizing the residual lung function.

The Effect Of Thermogenic Nutritional Supplementation On Resting Metabolism In College-age Females

BACKGROUND: Global increases in the incidence of obesity and the ensuing clinical co-morbidities has increased interest in the use of thermogenic supplements formulated to increase resting metabolism to increase energy expenditure and fat utilization. PURPOSE: The purpose of this study was to assess the effect of new capsaicin-based thermogenic supplements on resting oxygen consumption (VO2), carbon dioxide production (VCO2) and respiratory quotient (RQ). METHODS: Twenty-two untrained females (21.1±4.2 years) visited the lab on six occasions for measurements of pre-supplementation (PRE) resting energy expenditure (REE) for 30-60 min followed by the ingestion of a placebo or supplement (Shred, Shred 2.0, Capsimax 50, Capsimax 100, Capsimax 200) with at least three days separating conditions. Resting VO2, VCO2, and RQ were re-assessed for 90-120 minutes post-supplementation (POST). Changes in metabolic markers between treatment groups and over time were assessed in 5-minute intervals over the course of the 90-minute assessment using a two-way repeated measures ANOVA. RESULTS: PRE VO2 (2.5 ± 0.3 ml•kg-1•min-1; 0.21±0.03 L•min-1), VCO2 (0.18 ± 0.03 L•min-1), and RQ (0.85 ± 0.06) were lower than any given 5-minute interval POST (p<0.05). VO2 (ml•kg-1•min-1) was elevated at 5 min POST (2.99 ± 0.5 ml•kg-1•min-1) compared to each subsequent 5 min interval (p<0.05) with no differences noted after 10 minutes (2.7 ± 0.4 ml•kg-1•min-1). VCO2 and VO2 (L•min-1) were elevated at 5 min POST compared to subsequent 5-minute intervals until 80 min (VCO2; 0.22 ± 0.04 to 0.19 ± 0.03 L•min-1) and 70 min (VO2; 0.25 ± 0.04 to 0.23 ± 0.03 L•min-1; p<0.05). There were no changes in VCO2 at 10 minutes (0.19 ± 0.03 L•min-1) compared to any other time point POST. VO2 (L•min-1) briefly increased from 35-45 minutes POST (0.23 ± 0.04 L•min-1) compared to 20 min POST (0.22 ± 0.03 L•min-1; p=0.002); no further changes occurred after 45 minutes. There were no changes in RQ during POST. There were no interaction effects (time*treatment) or treatment differences in metabolic markers. CONCLUSIONS: Observed time effects are postulated as a result of the elevated REE caused by changes in subject position during supplement consumption, rather than supplementation. This study suggests that new thermogenic supplementation has no effect on metabolism.

MON-586 Gut Hormones Response to 24-H High Carbohydrate Overfeeding Is a Determinant of Metabolic Adaptation to Carbohydrate Intake in Healthy Individuals

Background: We previously demonstrated that short-term (24h) changes in carbohydrate (CARBOX) or fat oxidation rates in response to overfeeding diets with different macronutrient content are highly correlated within an individual, suggesting the existence of human metabolic phenotypes (carbohydrate vs. fat oxidizers). Gut hormones have a role in feeding and substrate oxidation, thus we investigated if the changes in gut hormones concentration during overfeeding diets or fasting explain the degree of metabolic flexibility in healthy humans.Methods: While residing in our clinical research unit, 67 healthy, weight-stable volunteers (37±10y, BMI: 26±4 kg/m2, body fat: 28±10%; mean±SD, 54 men) with normal glucose regulation had 24-h EE measurements in a whole-room indirect calorimeter during energy balance (EB, diet: 50% carbohydrate, 20% protein), three overfeeding diets, and fasting in a crossover design. The overfeeding diets (200% of weight-maintaining energy requirements) included diets with 20%-protein [50%-carbohydrate (SOF), 75%-carbohydrate (CNP), and 60%-fat (FNP)]. Metabolic flexibility was determined by the difference between respiratory quotient (RQ) during overfeeding/fasting from EB conditions. Plasma GLP-1, PYY, PP, and total ghrelin concentrations were measured by ELISA after an overnight fast the morning of and after each diet. Results: PYY increased after all overfeeding diets (3.4±13.1, 7.0±16.2, and 7.6±14.4 pg/mL; all p<0.05, SOF, CNP and FNP respectively) and decreased with fasting (-11.6±14.2 pg/mL; p<0.001). GLP-1 increased after fasting (2.7±5.8 pg/mL; p<0.001) and FNP (1.3±4.5 pg/mL; p=0.02) and decreased with CNP (-0.9±6.3 pg/mL; p=0.04). PP only increased after fasting (92.8±133.4 pg/mL; p<0.001), while ghrelin decreased with SOF (-31.3±108 pg/mL; p=0.02) and CNP (-43.1±120 pg/dL; p=0.005) but not with FNP (p=0.51). After adjustment for body composition and other known EE determinants, no hormonal changes were associated with the change in 24-h EE in any diet (all p>0.05); however, during CNP greater decreases in GLP1, PYY, and Ghrelin were associated with less increase in 24-h RQ (all r>0.25; all p<0.05) while greater decrease in PP was associated with larger increase in 24-h RQ (r=-0.31, p=0.01). Specifically, greater increase in CARBOX during CNP was positively associated with the changes in GLP-1 (r=0.30; p=0.02) and Ghrelin (r=0.32, p=0.01). In a linear model, only the change in GLP-1, PP, and Ghrelin concentrations during CNP were independent predictors of the change in RQ [β=0.003; -0.0001; and 0.000006 per 1 pg/mL increase each, p=0.008; 0.02 and 0.02 respectively], after accounting for age and sex. Conclusion: In a carbohydrate rich environment, individuals with normal glucose regulation who maintain GLP-1 and ghrelin levels are better adapted to metabolize this type of diet.

Effects of a whole diet approach on metabolic flexibility, insulin sensitivity and postprandial glucose responses in overweight and obese adults - A randomized controlled trial.

Metabolic flexibility is the ability to adapt fuel oxidation to fuel availability. Metabolic inflexibility has been associated with obesity, the metabolic syndrome and insulin resistance, and can be improved by exercise or weight loss. Dietary changes can modulate metabolic flexibility; however, the effect of a whole diet approach on metabolic flexibility has never been studied. Therefore, our objective was to assess the effect of a healthy diet (HD), as compared to a typical Western diet (WD), on several fasting and postprandial markers of metabolic flexibility and insulin sensitivity. In this parallel randomized trial, overweight or obese men and women (50-70 years; BMI 25-35kg/m2) consumed a healthy diet (HD; high in fruits and vegetables, pulses, fibers, nuts, fatty fish, and low in high-glycemic carbohydrates; n=19) or a typical Western diet (WD; n=21) for six weeks, following a two-week run-in period. The change in respiratory quotient upon insulin stimulation (ΔRQ), and insulin sensitivity, expressed as the M-value, were both determined with a hyperinsulinemic euglycemic clamp. Additionally, other fasting and postprandial markers of metabolic flexibility were assessed during a 5-h high-fat high-glycemic mixed meal challenge. ΔRQ (p=0.730) and insulin sensitivity (p=0.802) were not significantly affected by diet. Postprandial RQ did also not show significant differences (p=0.610), whereas postprandial glucose excursions were significantly higher in the HD group at T30 (p=0.014) and T45 (p=0.026) after mixed meal ingestion (p=0.037). Fasting glucose (p=0.530) and HbA1c (p=0.124) remained unchanged, whereas decreases in fasting insulin (p=0.038) and the HOMA-IR (p=0.050) were significantly more pronounced with the HD. A healthy diet for six weeks, without further life-style changes, did not improve metabolic flexibility and whole-body insulin sensitivity, when compared to a Western-style diet. It remains to be determined whether the short time increase in postprandial glucose is physiologically relevant or detrimental to metabolic health. This trial was registered at clinicaltrials.gov as NCT02519127.

Metabolic inflexibility in women with polycystic ovary syndrome: a systematic review

Polycystic ovary syndrome (PCOS) is a risk factor for dysglycemia, insulin resistance, and type 2 Diabetes Mellitus (T2DM). Inefficient energy oxidation, metabolic inflexibility, is a marker of blunted metabolism. We conducted a systematic review on metabolic inflexibility in women with PCOS. We searched MEDLINE, EMBASE and Cochrane central (inception-October 2018) for studies evaluating metabolic inflexibility and reporting on changes in Respiratory Quotient (ΔRQ). We extracted data and assessed quality using The Newcastle–Ottawa Scale. We included five prospective cohort studies (461 women). Three compared PCOS women to unaffected subjects, one to women with obesity or T2DM, and one to adolescent girls; all had medium quality. Three studies showed higher metabolic inflexibility in women with PCOS (ΔRQ range 0.05–0.098) compared to unaffected subjects. Women with PCOS had similar metabolic inflexibility compared to those with T2DM (ΔRQ 0.05 ± 0.03 vs 0.06 ± 0.04, p = .98) and obesity (p = .06). Inflexibility was higher in hyperandrogenemic women with PCOS (ΔRQ 0.091 ± 0.060 vs 0.120 ± 0.010, p = .014). ΔRQ was lower in PCOS women with insulin resistance vs those with normal insulin sensitivity (0.04 ± 0.02 vs. 0.07 ± 0.04, p = .007). In conclusion, women with polycystic ovary syndrome appear to have higher metabolic inflexibility associated with hyperandrogenemia and insulin resistance.

Cardiovascular Outcomes of Diet Counseling

Context: The leading cause of death in the U.S. is heart disease with obesity as the major correlate and, some believe, Cause: Obesity is caused by eating behaviors. The U.S. Preventive Services Task Force notes the need for, yet absence of, randomized controlled trials of behavior modification interventions for cardiovascular disease endpoints. Objectives: To modify habitual dietary behaviors with counseling, to assess retention of the resulting habits, and to compare cardiovascular effects of such modifications under diets differing in fat content. Design: One-year randomized controlled trial of three diet behavior interventions for cardiovascular and behavioral end-points with intermediate surrogate end-points enabling intent-to-treat analysis. Setting: Prairie States private cardiology practice. Participants: One hundred and twenty referrals screened for: cardiovascular co-morbidity, heart medication, and informed agreement. Intervention: One hour of diet protocol initial individual instruction and one half-hour of individual self-efficacy counseling every six weeks thereafter for one year. Main outcome measures: The primary cardiovascular measure was SPECT device measured physiologic coronary blood flow. Retention of modified habits was assessed with four-month post-study measurement of changes in Respiratory Quotient as a menu selection index and in Body Mass Index as a portion control index. Surrogate endpoints were weight, BMI, lipids and other standard blood chemistry indices. Results: Participant attrition, zero. Changes in coronary blood flow were correlated with diet protocol, R (95%CI)=0.48 to 0.69, p=2.4 x 10-12. Ischemia improved significantly under a lowered fat protocol and worsened significantly under lowered carbohydrate conditions. Surrogate endpoints, weight and blood chemistry, showed similar correlations, p&lt;10-11. Four months post-study, lowered fat dieters had retained their intervention modified behaviors while lowered carbohydrate and vegan dieters had changed, R (95%CI)=0.53 to 0.74, p=2.5 x 10-14 for portion control and R (95%CI)=0.76 to 0.88, p&lt;2.2 x 10-16 for menu selection.

1918-P: Carbohydrate and Fat Oxidation Fasting and in Response to a Hyperinsulinemic Clamp is Similar in Obese Youth Regardless of PCOS Status

Whole-body metabolic flexibility (MF), i.e., switching substrate oxidation between fasting and fed states often becomes abnormal with insulin resistance (IR). Data regarding MF in women with PCOS, whom often have IR, are mixed and confounded by varied diets and habitual physical activity. No study has assessed MF in response to a multi-phase hyperinsulinemic-euglycemic clamp in PCOS females relative to non-PCOS with similar habitual physical activity and controlled diet. Adolescent girls with obesity and PCOS (age 14.9 ± 1.5 years; BMI 35 ± 4 kg/m2), 10 obese controls (age 13.5 ± 1.3; BMI 32 ± 2) and 13 normal BMI PCOS (age 16.2 ± 1.5; BMI 22.8 ± 2) were included. All girls were sedentary per questionnaire and 7 day accelerometry. A 4-phase hyperinulinemic-euglycemic clamp (basal, 10, 16 and 80 mU/m2/min of insulin) including glucose and glycerol tracers was performed. Glucose rate of disappearance (Rd), glycerol rate of appearance (Ra) and respiratory quotient (RQ) were assessed during each clamp phase. MF was defined as a change in RQ from baseline to each phase (ΔRQ). Basal RQs were not different between groups. Lean PCOS had higher ΔRQ at phase 10 compared to obese PCOS (p=0.005) and obese controls (p=0.003). All groups had similar ΔRQs at 16 and 80 phases. In multivariable regression models, Δ 10 glycerol Ra (Δ from baseline to 10 phase) was associated with phase 10 ΔRQ, independent of age and BMI (p=0.04); Δ 80 glycerol Ra and Δ 80 glucose Rd were associated with phase 80 ΔRQ, independent of age and BMI (p=0.048). Sedentary obese adolescents regardless of PCOS status have lower MF compared to lean PCOS during the low insulin dose which was associated with whole body lipolysis. However, this difference is not found during the high insulin dose, suggesting obese girls have only subtle defects in MF. Further, PCOS is not associated with lower MF once diet and habitual activity are matched. Disclosure P. Wiromrat: None. C.A. Rynders: None. K.J. Nadeau: None. M. Cree-Green: None. Funding American Diabetes Association (7-11-CD-08 to K.J.N.); American Heart Association (13CRP14120015); Thrasher Research Fund; National Center for Research Resources Colorado (TL1TR002533); Pediatric Endocrinology Society; National Institute of Diabetes and Digestive and Kidney Diseases (T32DK063687, K23DK107871)

A Single Dose of Goji Berries Does Not Affect Postprandial Energy Expenditure and Substrate Oxidation in Healthy, Overweight Men.

Background and Aim Increasing energy expenditure is an effective strategy for the prevention of obesity. In this respect, Lycium barbarum (goji berry) is of interest, as it has been shown to increase postprandial oxygen consumption. Although this suggests that energy expenditure was also increased, energy expenditure and substrate oxidation can only be assessed accurately when both oxygen consumption and carbon dioxide production are measured. We therefore investigated the effects of a single dose of Lycium barbarum fruit on postprandial energy expenditure and substrate oxidation in a randomized, double-blind crossover trial. In addition, markers of lipid and glucose metabolism were measured. Methods Seventeen healthy, overweight men received in a random order a meal containing 25 grams of dried Lycium barbarum fruit or a control meal matched for caloric content and macronutrient composition. Energy expenditure and the respiratory quotient were determined using indirect calorimetry before and up to 4 hours after meal intake. Blood was sampled before and after meal intake at regular intervals for analyses of plasma glucose, serum triacylglycerol, and free fatty acid concentrations. Results Energy expenditure significantly increased after the Lycium barbarum and control meal, but no differences were found between the meals (p=0.217). Postprandial changes in respiratory quotient (p=0.719) and concentrations of glucose (p=0.663), triacylglycerol (p=0.391), and free fatty acids (p=0.287) were also not affected by Lycium barbarum intake. Conclusions A single dose of Lycium barbarum does not affect postprandial energy expenditure, substrate oxidation, and markers for lipid and glucose metabolism in healthy, overweight men.

Family History of Diabetes Does Not Affect Exercise-Induced Improvements in Insulin Sensitivity and Metabolic Flexibility

A family history of diabetes (FH+) is considered a risk factor to develop insulin resistance and type 2 diabetes. However, it is not known whether exercise induced improvement in insulin sensitivity (IS) and metabolic flexibility (MF) are impacted by a FH+, compared to those without (FH-). PURPOSE: To determine if a FH+ limits exercise induced improvements in IS, MF, body composition, and strength following an 8-week combined aerobic and resistance training intervention. METHODS: 19 sedentary, normoglycemic, Mexican-American males underwent 8 weeks of combined exercise training 3 times/week (35-min aerobic & 45-min resistance training/session). A controlled diet was provided 5 days before pre/post intervention tests. IS was assessed by hyperinsulinemic euglycemic clamp. MF was assessed by change in respiratory quotient (ΔRQ) at the insulin stimulated state of the clamp compared to the fasted state. Body composition was measured using DXA. Upper/lower body strength were measured by 1 repetition maximum bench press and leg strength dynamometer. RESULTS: IS significantly improved in both groups (FH- 2.95±31 to 3.84±0.31ml/kg estimated mean body size (EMBS), p=0.03; FH+ 3.6±0.5 to 4.8±0.5ml/kg EMBS; p=0.002). MF significantly improved in both groups (FH- 0.72±0.009 to 0.78±0.008, p=0.001; FH+ 0.70±0.01 to 0.80±0.02, p=0.0001). Fat free mass significantly improved in both groups (FH- 56.6±2.1 to 58.5±2.1kg, p=0.01; FH+ 51.8±1.95 to 53.4±1.79kg, p=0.01). Upper body strength (FH- 172.78±20.95 to 200.56±20.74lb, p=0.0001; FH+ 136.5±14.06 to 168.33±15.29lb, p=0.0001) and lower body strength (FH- 368.89±31.02 to 431.11±22.58lb, p=0.007; FH+ 341.0±22.03 to 412.78±16.22lb, p=0.0001) significantly increased in both groups. Degrees of improvement in IS was not different between groups (FH- 28.3±13.6% vs. FH+ 41.66±11.9%; p>0.05). CONCLUSION: FH+ is not a limiting factor for exercise induced improvements in IS, MF, body composition, and strength in normoglycemic Mexican Americans.

Pioglitazone-induced improvements in insulin sensitivity occur without concomitant changes in muscle mitochondrial function

AimsPioglitazone (Pio) is known to improve insulin sensitivity in skeletal muscle. However, the role of Pio in skeletal muscle lipid metabolism and skeletal muscle oxidative capacity is not clear. The aim of this study was to determine the effects of chronic Pio treatment on skeletal muscle mitochondrial activity in individuals with type 2 diabetes (T2D). Materials and MethodsTwenty-four participants with T2D (13M/11F 53.38±2.1years; BMI 36.47±1.1kg/m2) were randomized to either a placebo (CON, n=8) or a pioglitazone (PIO, n=16) group. Following 12weeks of treatment, we measured insulin sensitivity by hyperinsulinemic–euglycemic clamp (clamp), metabolic flexibility by calculating the change in respiratory quotient (ΔRQ) during the steady state of the clamp, intra- and extra-myocellular lipid content (IMCL and EMCL, respectively) by 1H magnetic resonance spectroscopy (1H-MRS) and muscle maximal ATP synthetic capacity (ATPmax) by 31P-MRS. ResultsFollowing 12weeks of PIO treatment, insulin sensitivity (p<0.0005 vs. baseline) and metabolic flexibility (p<0.05 vs. CON) significantly increased. PIO treatment significantly decreased IMCL content and increased EMCL content in gastrocnemius, soleus and tibialis anterior muscles. ATPmax was unaffected by PIO treatment. ConclusionsThese results suggest that 12weeks of pioglitazone treatment improves insulin sensitivity, metabolic flexibility and myocellular lipid distribution without any effect on maximal ATP synthetic capacity in skeletal muscle. Consequently, pioglitazone-induced enhancements in insulin responsiveness and fuel utilization are independent of mitochondrial function.

Adipocyte Versus Somatotrope Leptin: Regulation of Metabolic Functions in the Mouse.

Leptin regulates food intake and energy expenditure (EE) and is produced in adipocytes, the pituitary, and several other tissues. Animals that are leptin or leptin receptor deficient have major metabolic complications, including obesity. This study tests the hypothesis that the pituitary somatotrope may contribute a source of leptin that maintains some of these metabolic functions. We created 2 different tissue-specific leptin knockout animals: a Somatotrope-Lep-null model and an Adipocyte-Lep-null model. Metabolic analysis of both models, along with a global deletion model, was performed. The Somatotrope-Lep-null animals had fewer somatotropes, and females had a 76% decrease in serum prolactin. During the dark (feeding) phase, females had a 35% increase in ambulation coupled with a 4% increase in EE. Mutants showed no change in food intake or weight gain and EE was unchanged in males. During the light (sleep) phase, Somatotrope-Lep-null mutant males had lower EE and females continued to have higher EE. The respiratory quotients (RQs) of mutants and littermate controls were decreased in males and increased in females; all were within the range that indicates predominant carbohydrate burning. The massively obese Adipocyte-Lep-null animals, however, had significant increases in food intake, sleep, and increased EE, with decreased activity. Changes in RQ were sexually dimorphic, with female mutants having higher RQ and males having decreased RQ. We conclude that both adipocyte and somatotrope leptin contribute to the metabolic homeostasis of the mouse, and that extraadipocyte sources of leptin cannot overcome the major metabolic challenges seen in these animals.