The impact of leucine supplementation on body composition and glucose tolerance following energy restriction: an 8-week RCT in adults at risk of the metabolic syndrome.

BACKGROUND: L-Leucine (Leu) supplementation may benefit fat-free mass (FFM) per se and glucose metabolism. OBJECTIVES: To determine whether Leu supplementation during energy restriction blunted the loss of FFM, enhanced the loss of fat mass (FM) and improved glucose tolerance. DESIGN: Thirty-seven adults, aged 20-65 years, with increased waist circumference and at least one other metabolic syndrome (MetS) component, were selected. We employed a two-arm parallel, double blind, randomized control trial (RCT) design. Participants were randomly assigned to an intervention group (leucine - 3 g/d) or placebo (lactose - 2.67 g/d), while following an individualised energy restricted diet for an 8-week period. Detailed body composition (DEXA), oral glucose tolerance test (OGTT), insulin and components of MetS were measured before and after the trial. Analysis of covariance (ANCOVA) assessed the effect of Leu on an intention-to-treat (ITT) principle. Bootstrapping method with 1000 bootstrap samples was used to derive parameter estimates, standard errors, p-values, and 95% confidence intervals for all outcomes. RESULTS: Adjusted for baseline values and other covariates, FFM (p = 0.045) and lean tissue mass (LTM) (p = 0.050) were significantly higher following Leu. These outcomes were modified by a significant treatment x sex interaction that indicated Leu had the greater effect in men. However, on adjustment for body composition changes, there was no difference in insulin sensitivity, oral glucose tolerance, or change in MetS components following Leu. CONCLUSION: Short-term leucine supplementation during energy restriction resulted in a greater preservation of FFM and LTM particularly in men, but did not impact glucose metabolism.

Higher fasting fibroblast growth factor 21 was associated with a greater decline in postprandial blood pressure.

BACKGROUND: A fall in blood pressure (BP) following a meal is well known and is usually a transient phenomenon, due to appropriate cardiovascular adjustments. Older individuals and those with high BP experience a greater postprandial fall that can manifest as postprandial hypotension (PPH). Fibroblast growth factor 21 (FGF21) is positively associated with BP, and is known to increase after meal ingestion. We explored whether fasting FGF21 or its postprandial change would be associated with meal induced BP change, after accounting for several covariates. METHODS: Eighty-three Western Australian adults were studied. Supine resting BP was recorded and an oral glucose test was administered. Serial measurements of systolic BP (SBP) and diastolic BP (DBP) were then made in duplicate every 30 min up to 120 min. Fasting and 120 min blood samples were analysed for FGF21 and clinical chemistry. Multiple linear regression analyses of the incremental area under curve of postprandial SBP and DBP was conducted on 12 known determinants. RESULTS: The final parsimonious model based on backward regression of postprandial SBP included fasting SBP, gender, fasting insulin and fasting FGF21 (ß = -0.009 (95% confidence interval (CI): 0.017, -0.002, P = 0.015)). For postprandial DBP these included fasting DBP, gender, fasting glucose, fasting insulin and fasting FGF21 (ß = -0.005; 95% CI: 0.010, -0.001, P = 0.021). CONCLUSIONS: A higher fasting FGF21, independent of glucose and insulin, was associated with a greater postprandial decline in SBP and in DBP.

Triglycerides and systolic blood pressure negatively mediate the direct relationship of vitamin D status to resting energy expenditure: A cross sectional analysis.

BACKGROUND AND AIMS: We determined whether individual components of metabolic syndrome (MetS) mediated the direct association of vitamin D status (25OHD) on resting energy expenditure (REE). METHODS: Multiple linear regression determined predictors of REE from data on 180 men and women from two ethnic groups. We then modelled a mediation pathway through components of MetS on the direct association between 25OHD and REE. The mediation modelling used the PROCESS SPSS Macro (version 4.0) based on 5000 bootstrapped samples, with the adjustment for different sets of covariates. RESULTS: REE was significantly predicted by age, fat mass (FM), fat free mass (FFM), ethnicity, inverse ln insulin, 25OHD, triglycerides (TG), systolic blood pressure (SBP) and, to some extent, by time of REE measurements (p < 0.094). Adjustment for all these covariates, resulted in a negative indirect mediation effect of TG [ß coefficient (bootstrapped SE): 0.95 (0.519); bootstrapped 95% CI: 2.172, -0.165; p < 0.05] and a concurrent negative mediation of SBP [ß coefficient (bootstrapped SE): 0.72(0.484); bootstrapped 95% CI: 1.851, -0.011; p < 0.05]. There remained a positive direct pathway from 25OHD to REE [ß coefficient (S.E): 4.715 (2.129); p = 0.028], however the total effect of 25OHD was dampened [ß coefficient (S.E): 3.04 (2.126); p = 0.154]. CONCLUSIONS: Independent of insulin sensitivity, a negative mediation by TG and SBP dampened the overall effect of 25OHD on REE.

Cross sectional determinants of VO2 max in free living Iranians: Potential role of metabolic syndrome components and vitamin D status.

BACKGROUND AND AIMS: The purpose of the study was to evaluate the determinants of cardiorespiratory fitness (CRF) in Iranian adults and the potential contribution of vitamin D status. METHODS: In this cross-sectional study 264 cases (116 men and 147 women aged 18-70 years old were participated. Maximal oxygen consumption (VO2 max) was measured by the Bruce protocol utilizing treadmill exercise testing. Anthropometric data, body composition and fasting blood glucose and lipid concentrations were measured. Serum levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were assessed using enzyme-linked immunosorbent assay. Stepwise linear regression analysis was applied to determine significant predictors of VO2 peak. We tested non-linear (quadratic and cubic terms) versus linear association of adjusted (for determinants) VO2 max and vitamin D levels. RESULTS: Multiple regression results showed that fat free mass, HDL-C and physical activity, waist circumference, age and sex were determinants of VO2 peak. All of these explained the 65.3% of VO2 peak. There was a non-linear cubic association (R2 = 0.03, p = 0.046) between serum 25(OH)D and adjusted VO2 peak in which 25(OH)D in people with a high 25(OH)D levels (>60 nmol/L), had better fitness and those with serum 25(OH) less than 20 nmol/L. We found no linear and non-linear associations between serum 1,25(OH)2 D and adjusted VO2 max. CONCLUSIONS: Our results showed that waist circumference and HDL-C, as components of metabolic syndrome, contribute ∼2% to the variance in VO2 max. Moreover, high concentrations of 25(OH)D but not 1,25(OH)2 D may make additional contributions to CRF.

Hypothesized pathways for the association of vitamin D status and insulin sensitivity with resting energy expenditure: a cross sectional mediation analysis in Australian adults of European ancestry.

BACKGROUND: The role of vitamin D in human energy expenditure requires confirmation. We explored whether insulin sensitivity (IS)/insulin resistance (IR) mediated the association of vitamin D status (25OHD) on resting energy expenditure (REE). METHODS: REE, body composition (by DEXA) and clinical biochemistry of 155 Australian men and women were collated. A hypothesized mediation pathway through IS/IR on the direct association between 25OHD and REE was modeled, using three surrogate indices of IS/IR: McAuley's insulin sensitivity index (McA), Quantitative insulin sensitivity check index (QUICKI) and triglyceride to glucose ratio (TYG). The modeling was performed on PROCESS SPSS Macro (version 4.0) based on 5000 bootstrapped samples, with and without the adjustment for covariates. RESULTS: Unadjusted models indicated a sizeable negative mediation by all IS/IR indices but no significant direct effect of 25OHD on REE. On adjustment for covariates, a negative indirect mediation effect of McA [ß coefficient (SE) -2.1(0.821); bootstrapped 95% CI:-3.934, -0.703; p < 0.05] and a similar negative mediation of TYG [-1.935 (0.780); bootstrapped 95% CI: (-3.679, -0.622; p < 0.05] was observed. These models also showed a positive direct effect of 25OHD on REE. In contrast, QUICKI made a smaller contribution to the total effect though in the same direction as the other two measures [-0.783 (0.534); bootstrapped 95% CI: (-1.939, 0.134; P > 0.05]. CONCLUSIONS: A sizeable, partial, negative mediation of IS/IR on the direct relationship between 25OHD and REE, dampened the total effect of vitamin D on REE. Validation of the proposed causal framework would clarify vitamin D's role in human energy metabolism.

The Association between Exposure to Residential Indoor Volatile Organic Compounds and Measures of Central Arterial Stiffness in Healthy Middle-Aged Men and Women.

It is well reported that individuals spend up to 90% of their daily time indoors, with between 60% to 90% of this time being spent in the home. Using a cross-sectional study design in a population of 111 healthy adults (mean age: 52.3 ± 9.9 years; 65% women), we investigated the association between exposure to total volatile organic compounds (VOCs) in indoor residential environments and measures of central arterial stiffness, known to be related to cardiovascular risk. Indoor VOC concentrations were measured along with ambulatory measures of pulse pressure (cPP), augmentation index (cAIx) and cAIx normalized for heart rate (cAIx75), over a continuous 24-h period. Pulse wave velocity (cfPWV) was determined during clinical assessment. Multiple regression analysis was performed to examine the relationship between measures of arterial stiffness and VOCs after adjusting for covariates. Higher 24-h, daytime and night-time cAIx was associated with an interquartile range increase in VOCs. Similar effects were shown with cAIx75. No significant effects were observed between exposure to VOCs and cPP or cfPWV. After stratifying for sex and age (≤50 years; >50 years), effect estimates were observed to be greater and significant for 24-h and daytime cAIx in men, when compared to women. No significant effect differences were seen between age groups with any measure of arterial stiffness. In this study, we demonstrated that residential indoor VOCs exposure was adversely associated with some measures of central arterial stiffness, and effects were different between men and women. Although mechanistic pathways remain unclear, these findings provide a possible link between domestic VOCs exposure and unfavourable impacts on individual-level cardiovascular disease risk.

Lack of a relationship between vitamin D status and resting metabolic rate in Iranian adults.

OBJECTIVES: Studies suggest a positive relationship between 25-hydroxy vitamin D (25(OH)D)) and resting metabolic rate (RMR). We aimed to determine whether this relationship was also true of populations with very low vitamin D status. METHODS: Fat mass (FM) and fat free mass (FFM) were determined from multifrequency bioimpedance analysis (InBody 720, Korea). RMR was based on indirect calorimetry (Cortex Metalyser 3B, Germany). Fasting blood measurements of 25(OH)D concentration, glucose and triglycerides were measured. Data were analyzed separately on men and women by tertile of vitamin D status and multiple linear regression analysis. RESULTS: Two hundred and sixty-three subjects (115 males; 148 females) with a mean age of 37 years and mean %body fat of 30.5% were studied. In women but not men, age, body weight, waist circumference, FM, and FFM increased significantly across tertiles of 25(OH)D. However, there was no difference in unadjusted or adjusted RMR across tertiles of 25OHD in both women and men. Stepwise forward regression analysis showed that age and FFM in men, age and FM in women but not by 25(OH)D, were determinants of RMR. In addition, RMR adjusted for age, sex, FM, FFM and triglyceride-glucose index did not relate to 25(OH)D when linear (r = 0, P = .98), quadratic (r = 0.008, P = .34), or cubic (r = 0.010, P = .43) relationships were tested. CONCLUSIONS: Residual variation in RMR did not relate to vitamin D status in a group of Iranian adults with very low vitamin D status. Future studies could examine whether such a relationship holds true, after the normalization of vitamin D status.

Serum Vitamin D status is associated with increased blastocyst development rate in women undergoing IVF.

RESEARCH QUESTION: To determine the relationship between vitamin D (VitD) status and embryological, clinical pregnancy and live birth outcomes in women undergoing IVF. DESIGN: Cross-sectional, observational study conducted at a university-affiliated private IVF clinic. A total of 287 women underwent 287 IVF cycles and received a fresh embryo transfer. Patients had their serum 25-hydroxyvitamin D2/D3 (VitD) determined on the day of oocyte retrieval, which was analysed in relation to blastocyst development rate, clinical pregnancy and live birth outcomes. RESULTS: In stepwise, multivariable logistic regression models, increases in blastocyst development rate, number and quality, along with embryo cryopreservation and utilization rates were associated with women with a sufficient VitD status (≥20 ng/ml). For a single increase in the number of blastocysts generated per cycle or embryos cryopreserved per cycle, the likelihood for the patient to be VitD sufficient was increased by 32% (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.10-1.58, P = 0.002 and OR 1.33, 95% CI 1.10-1.60, P = 0.004, respectively). Clinical pregnancy (40.7% versus 30.8%, P = 0.086) and live birth rates (32.9% versus 25.8%, P = 0.195) in the sufficient VitD group versus the insufficient group were not significantly different and VitD sufficiency was not significantly associated with these outcomes. CONCLUSION: A strong relationship was observed between blastocyst development and VitD sufficiency. However, there was no association between VitD and clinical pregnancy or live birth outcomes. Further larger studies are needed to investigate whether the observed effect on blastocyst development may have downstream implications on subsequent clinical pregnancy or live birth rates, and on a potential mechanism where sufficient VitD concentrations are linked to improved IVF outcomes.

High-dose thiamine supplementation may reduce resting energy expenditure in individuals with hyperglycemia: a randomized, double - blind cross-over trial.

BACKGROUND: Despite the crucial role of thiamine in glucose and energy metabolism pathways, there has been no published study examining the impact of thiamine on energy metabolism in humans. OBJECTIVE: To assess the effects of thiamine supplementation on resting energy expenditure (REE) in individuals with hyperglycemia. METHODS: Twelve hyperglycemic patients completed this double-blind, randomized trial, where all participants received both thiamine (300 mg/day) and matched placebo for 6 weeks in a cross-over manner. REE was assessed by indirect calorimetry. Anthropometric measurements, fasting and 2-h plasma glucose, and glucose-induced thermogenesis were also assessed at the beginning and on the completion of each six-week phase. RESULTS: Participants consuming thiamine supplements experienced a significant decrease in the REE assessed at week six compared to the baseline [mean (SE): 1478.93 (73.62) vs.1526.40 (73.46) kcal/d, p = 0.02], and the placebo arm (p = 0.002). These results did not change significantly after adjusting for the participants' body weight and physical activity as potential confounders. Six-week intervention had no significant effect on the participants' body weight or waist circumference, in either supplement or placebo arms (all p values>0.05). However, correlation analysis highlighted significant positive relationships between the changes in REE, and those in fasting (rs = 0.497, p = 0.019) and 2-h plasma glucose (rs = 0.498, p = 0.018) during the six-week intervention period. CONCLUSION: Supplementation with high-dose thiamine may attenuate REE in patients with impaired glucose regulation. Our findings suggest that the impact of thiamine on REE may in part be explained by improved glycemic control. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12611000051943. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12611000051943.

Associations Between Sub-Clinical Markers of Cardiometabolic Risk and Exposure to Residential Indoor Air Pollutants in Healthy Adults in Perth, Western Australia: A Study Protocol.

BACKGROUND: A growing body of epidemiological and clinical evidence has implicated air pollution as an emerging risk factor for cardiometabolic disease. Whilst individuals spend up to two-thirds of daily time in their domestic residential environment, very few studies have been designed to objectively measure the sub-clinical markers of cardiometabolic risk with exposure to domestic indoor air pollutants. This cross-sectional study aims to investigate associations between the components of domestic indoor air quality and selected sub-clinical cardiometabolic risk factors in a cohort of healthy adults living in Perth, Western Australia. METHODS: One hundred and eleven non-smoking adults (65% female) living in non-smoking households who were aged between 35-69 years were recruited for the project. Study subjects were invited to participate in all sections of the study, which included: Domestic indoor air monitoring along with the concurrent 24 h ambulatory monitoring of peripheral and central blood pressure and measures of central hemodynamic indices, standardized questionnaires on aspects relating to current health status and the domestic environment, a 24 h time-activity diary during the monitoring period, and clinic-based health assessment involving collection of blood and urine biomarkers for lipid and glucose profiles, as well as measures of renal function and an analysis of central pulse wave and pulse wave velocity. RESULTS: This study provides a standardized approach to the study of sub-clinical cardiometabolic health effects that are related to the exposure to indoor air pollution. CONCLUSION: The findings of this study may provide direction for future research that will further contribute to our understanding of the relationship that exists between indoor air pollution and sub-clinical markers of cardiometabolic risk.

Epidemiology and determinants of type 2 diabetes in south Asia.

Type 2 diabetes has rapidly developed into a major public health problem in south Asia (defined here as Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka) in recent decades. During this period, major lifestyle changes associated with economic transition, industrialisation, urbanisation, and globalisation have been key determinants in the increasing burden of non-communicable diseases. A decline in nutrition quality, reduced physical activity, and increased sedentary behaviours are reflected in the increasing prevalence of type 2 diabetes and related risk factors in the region. The International Diabetes Federation 2017 estimates of the prevalence of diabetes in adults in the region range from 4·0% in Nepal to 8·8% in India. The prevalence of overweight ranges from 16·7% in Nepal to 26·1% in Sri Lanka, and the prevalence of obesity ranges from 2·9% in Nepal to 6·8% in Sri Lanka. An increasing proportion of children, adolescents, and women are overweight or obese, leading to a heightened risk of type 2 diabetes. Ethnic south Asians present with greater metabolic risk at lower levels of BMI compared with other ethnic groups (referred to as the south Asian phenotype), with type 2 diabetes often developing at a younger age, and with rapid progression of diabetic complications. Because of the presence of multiple risk factors and a body composition conducive to the development of type 2 diabetes, south Asians should be aggressively targeted for prevention. In this Series paper, we detail trends in the prevalence of diabetes in the region and address major determinants of the disease in the context of nutrition and physical activity transitions and the south Asian phenotype.

Public health and health systems: implications for the prevention and management of type 2 diabetes in south Asia.

Many non-communicable chronic diseases, including type 2 diabetes, are highly prevalent, costly, and largely preventable. The prevention and management of type 2 diabetes in south Asia requires a combination of lifestyle changes and long-term health-care management. However, public health and health-care systems in south Asian countries face serious challenges, including the need to provide services to many people with inadequate resources, and substantial between-population and within-population inequalities. In this Series paper, we explore the importance and particular challenges of public health and health systems in south Asian countries (Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka) with respect to the provision of culturally appropriate lifestyle modification to prevent and manage diabetes, especially in resource-poor settings. Effective primary prevention strategies are urgently needed to counter risk factors and behaviours preconception, in utero, in infancy, and during childhood and adolescence. A concerted focus on education, training, and capacity building at the community level would ensure the more widespread use of non-physician care, including community health workers. Major investment from governments and other sources will be essential to achieve substantial improvements in the prevention and management of type 2 diabetes in the region.

Body fat, metabolic syndrome and hyperglycemia in South Asians.

The prevalence of overweight and obesity is escalating in South Asian countries. South Asians display higher total and abdominal obesity at a lower BMI when compared to Whites. Consequently, metabolic dysfunction leading to metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) will account for a majority of the health burden of these countries. In this review, we discuss those factors that contribute to MetS and T2DM in South Asians when compared to whites, focusing on adiposity. Abdominal obesity is the single-most important risk factor for MetS and its predisposition to T2DM. Excessive ectopic fat deposition in the liver (non-alcoholic fatty liver disease) has been linked to insulin resistance in Asian Indians, while the effects of ectopic fat accumulation in pancreas and skeletal muscle need more investigation. South Asians also have lower skeletal muscle mass than Whites, and this may contribute to their higher risk T2DM. Lifestyle factors contributing to MetS and T2DM in South Asians include inadequate physical activity and high intakes of refined carbohydrates and saturated fats. These are reflective of the recent but rapid economic transition and urbanization of the South Asian region. There is need to further the research into genetic determinants of dysmetabolism as well as gene x environment interactions. Collectively, MetS and T2DM have multi-factorial antecedents in South Asians and efforts to combat it through low-cost and socio-culturally appropriate lifestyle interventions need to be supported.

Vitamin D status is inversely associated with markers of risk for type 2 diabetes: A population based study in Victoria, Australia.

A growing body of evidence suggests a protective role of vitamin D on the risk of type 2 diabetes mellitus (T2DM). We investigated this relationship in a population sample from one Australian state. The data of 3,393 Australian adults aged 18-75 years who participated in the 2009-2010 Victorian Health Monitor survey was analyzed. Socio-demographic information, biomedical variables, and dietary intakes were collected and fasting blood samples were analyzed for 25, hydroxycholecalciferol (25OHD), HbA1c, fasting plasma glucose (FPG), and lipid profiles. Logistic regression analyses were used to evaluate the association between tertiles of serum 25OHD and categories of FPG (<5.6 mmol/L vs. 5.6-6.9 mmol/L), and HbA1c (<5.7% vs. 5.7-6.4%). After adjusting for social, dietary, biomedical and metabolic syndrome (MetS) components (waist circumference, HDL cholesterol, triglycerides, and blood pressure), every 10 nmol/L increment in serum 25OHD significantly reduced the adjusted odds ratio (AOR) of a higher FPG [AOR 0.91, (0.86, 0.97); p = 0.002] and a higher HbA1c [AOR 0.94, (0.90, 0.98); p = 0.009]. Analysis by tertiles of 25OHD indicated that after adjustment for socio-demographic and dietary variables, those with high 25OHD (65-204 nmol/L) had reduced odds of a higher FPG [AOR 0.60, (0.43, 0.83); p = 0.008] as well as higher HbA1c [AOR 0.67, (0.53, 0.85); p = 0.005] compared to the lowest 25OHD (10-44 nmol/L) tertile. On final adjustment for other components of MetS, those in the highest tertile of 25OHD had significantly reduced odds of higher FPG [AOR 0.61, (0.44, 0.84); p = 0.011] and of higher HbA1c [AOR 0.74, (0.58, 0.93); p = 0.041] vs. low 25OHD tertile. Overall, the data support a direct, protective effect of higher 25OHD on FPG and HbA1c; two criteria for assessment of risk of T2DM.

Postprandial changes in glucose oxidation and insulin sensitivity in metabolic syndrome: Influence of fibroblast growth factor 21 and vitamin D status.

OBJECTIVE: Metabolic inflexibility due to insulin resistance has been reported in metabolic syndrome (MetS). Fibroblast growth factor 21 (FGF21) and vitamin D status may improve insulin sensitivity. The aim of this study was to investigate glucose-induced thermogenesis and oxidation in MetS, and to examine whether changes in FGF21 or prevailing vitamin D status modulated defined metabolic parameters. METHODS: Forty-eight overweight and obese older adults (14 men, 34 women; ages 51 ± 15 y) were studied. Resting metabolic rate (RMR) and respiratory quotient (RQ) were measured before and intermittently for 2 h after an oral glucose tolerance test (OGTT). The total area under the curve (TAUC) was calculated. Insulin sensitivity index (ISI) was determined as 104/(insulin × glucose) for fasting and 2 h venous blood. Fat mass (FM) and fat free mass (FFM) were measured by dual-energy x-ray absorptiometry. Participants were grouped by metabolic syndrome (MetS+ for disease presence; MetS- when no disease was present) and by median 25 hydroxyvitamin D (OHD) concentration as VD_low and VD_high. 25 OHD was also tested as a continuous variable. A parsimonious 2 × 2 analysis of variance included age, FM, FFM and MetS × sex interaction. RESULTS: Adjusted RMR was similar between groups but an interactive effect of MetS and sex was noted. Fasting RQ was significantly different between vitamin groups (VD_low: 0.835 ± 0.008 versus VD_high: 0.810 ± 0.008; P = 0.024) and fasting ISI was significantly greater in MetS- compared with MetS+ (P = 0.037). Postglucose increases in thermogenesis, RQ, and FGF21 were significant, but ISI decreased. Adjusted postprandial TAUC_RQ (VD_low: 1.71 ± 0.01; VD_high: 1.74 ± 0.001; P = 0.041) and ISI_2 h (VD_low: 35.41 ± 0.21; VD_high: 101.90 ± 0.21; P = 0.001) were significantly different. Adjusted FGF21 was similar across all comparisons before and after OGTT. CONCLUSIONS: Higher vitamin D status, but not FGF21, was associated with greater postprandial glucose oxidation and improved insulin sensitivity.

Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells.

BACKGROUND: Vitamin D status [25(OH)D] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs). No study has tracked the seasonal variation of 25(OH)D and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry. MATERIAL AND METHODS: Whole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test) was performed using the Seahorse XFe96 flux analyser. 25(OH)D was assessed using the Architect immunoassay method. RESULTS: 25(OH)D increased by a median (IQR) of 14.40 (20.13)nmol/L (p<0.001) from winter to summer and was accompanied by significant improvements in indices of insulin sensitivity, McAuley's index (p=0.019) and quantitative insulin sensitivity check index (p=0.028). PBMC mitochondrial parameters basal respiration, non-mitochondrial respiration, ATP production, proton leak, and maximal respiration decreased in summer compared to winter. Similarly, PBMC glycolytic parameters glycolytic activity, glucose response, and glycolytic capacity were all reduced in summer compared to winter. There was also a trend for absolute resting metabolic rate (RMR) to decrease (p=0.066). Markers of systemic inflammation MCP-1, IL-6, IL-8, IL-10, and IL-12p70 decreased significantly in summer compared to winter. Participants who entered winter with a low 25(OH)D (<50nmol/L), had the greatest alteration in bioenergetic parameters in summer, relative to those with winter 25(OH)D concentrations of 50-75nmol/L or >75nmol/L. The absolute change in 25(OH)D was not associated with altered bioenergetics. CONCLUSION: Seasonal improvements in 25(OH)D was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OH)D in winter. The data warrants confirmation through cause and effect study designs.

The influence of ethnicity and glucose tolerance status on subjective hunger sensations and prospective food intake in overweight and obese Asian and European Australians.

AIMS: To examine the influence of ethnicity and glucose tolerance status on subjective sensations and food intake in overweight/obese Asian and European Australians. METHODS: 18 Asians and 26 Europids were classified as normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) based on serial measures of finger-prick glucose following an oral glucose tolerance test (OGTT). Subjective sensations of hunger and satiety were measured before and every 15min after the OGTT using a visual analogue scale (VAS). Food intake was measured covertly from consumption of a buffet style lunch and from self-maintained 24h food records. All serial measurements were converted into total area under the curve (TAUC) and comparisons adjusted for age, fat and fat-free mass. RESULTS: There was a significant difference interaction between ethnicity (ETH) and glucose tolerance (GTT) for subjective fullness, desire for food and prospective food intake. IGT Asians had significantly greater sensations of fullness, but lesser prospective food and desire to eat, as compared to other groups. However there were no differences in calorie and macronutrient intake at buffet lunch or over 24-h. CONCLUSION: Interactions between ethnicity and glucose tolerance status in subjective sensations did not transcribe to differences in prospective food intake.