Changes In Metabolic Variables Research Articles

Randomized comparison between a forced air system and warm water bath for resuscitation of neonatal hyperthermic calves with or without oral administration of caffeine.

Hypothermia is a cause of neonatal calf death in cold climates. Practical and effective rewarming methods are important for bovine health within affected regions. To compare the rewarming rate and blood analytes (glucose, lactate, and cortisol) of calves resuscitated with forced air with warm water bath, with or without oral administration of caffeine. Twenty healthy neonatal Holstein bull calves. In this randomized, prospective study, calves born healthy and without history of dystocia were cooled to 32°C rectal temperature then thermally resuscitated using either forced air rewarming or warm water bath (40°C) with or without oral administration of caffeine. Rectal temperatures were used to quantify recovery rate. Measurements of glucose, lactate, and cortisol were recorded for every 2°C change in rectal temperature. Rectal temperature decline (0.03°C per minute) and total cooling time (191.0 ± 33.3 minutes) did not significantly differ among treatment groups. Calves were successfully resuscitated to 38°C by either method. Time required to euthermia using warm water was significantly faster (0.1°C per minute; 64.3 ± 17.8 minute; P < .05) than forced air (0.05°C per minute; 123.1 ± 20.0 minutes). Caffeine had no significant effect on resuscitation rate (P = .14; 95% CI, -0.002 to 0.024) in either treatment; however, caffeine was associated with reduced time to euthermia by 8.3 and 10.8 minutes, respectively. Changes in metabolic variables (glucose, lactate, and cortisol), were inversely related to rectal temperature with no statistical significance among rewarming methods. Although warm water submersion is faster, forced air rewarming is an effective alternative for restoration of euthermia.

1571-P: Plasma FGF5 Concentration Correlates Better with Hepatic Steatosis, Blood Glucose, and Specific Plasma Free Fatty Acids than with Other Tissue Fat Accumulation

A few studies reported an association between fibroblast growth factor-5 (FGF5) and NAFLD. We aimed to elucidate the physiologic implication of FGF5 in NAFLD and obesity. A total of 180 subjects [(24 healthy controls and 156 patients with biopsy-proven NAFLD and/or hepatic fat content (HFC) 5% or more on MRI-PDFF] were included to assess association between HFC and various metabolic factors including body fat and plasma levels of glucose, insulin, FGF5, FGF21, oxyntomodulin, incretins, and some free fatty acids (FFAs). Additionally, we analysed a subgroup of obese patients who would undergo laparoscopic sleeve gastrectomy (LSG) (n=50) to see correlation between changes in metabolic variables related to body weight (BW) and HFC before and 6 months after surgery. Plasma FGF5 correlated better with blood glucose and HFC than with total body fat, HOMR-IR, and visceral fat. In relation to plasma FFAs, both FGF5 and HFC together showed a positive correlation with plasma FFAs such as palmitic acid, linolenic acid, and arachidonic acid, but had an inverse correlation with nervonic acid, docosanoic acid, tetracosanoic acid, and hexacosanoic acid. FGF5 level showed an independent association with blood glucose and MRI-PDFF after adjusting for multiple factors. After LSG, BW decreased by an average of 24.6%, while HFC decreased from 19.5% ± 9.1% to 5.7 ± 2.9%, p &amp;lt;0.01). Plasma FGF5 also decreased after LSG (1625.0 ± 656.8 pg/ml vs. 966.8 ± 339.9 pg/ml, p &amp;lt;0.01). The amount of plasma FGF5 change showed a significant correlation with changes in HFC and blood glucose. In conclusion, our results showed that plasma FGF5 level correlated well with HFC, blood glucose, and specific plasma FFAs and also decreased with the improvement of hepatic steatosis after bariatric surgery. Further researches on the causal relationship between FGF5, glucose and lipid metabolism, and NAFLD are needed. Disclosure D.Lee: None. I.Park: None. Funding National Research Foundation of Korea (2021R1A5A2030333, 2019R1I1A2A02062305)

Human-induced pluripotent stem cell-atrial-specific cardiomyocytes and atrial fibrillation.

Patient-specific human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs) may be produced, genome-edited, and differentiated into multiple cell types for regenerative medicine, disease modeling, drug testing, toxicity screening, and three-dimensional tissue fabrication. There is presently no complete model of atrial fibrillation (AF) available for studying human pharmacological responses and evaluating the toxicity of potential medication candidates. It has been demonstrated that hiPSC-aCMs can replicate the electrophysiological disease phenotype and genotype of AF. The hiPSC-aCMs, however, are immature and do not reflect the maturity of aCMs in the native myocardium. Numerous laboratories utilize a variety of methodologies and procedures to improve and promote aCM maturation, including electrical stimulation, culture duration, biophysical signals, and changes in metabolic variables. This review covers the current methods being explored for use in the maturation of patient-specific hiPSC-aCMs and their application towards a personalized approach to the pharmacologic therapy of AF.

Comparison of energy expenditure and substrate oxidation between walking and running in men and women.

[Purpose]The present study compared energy metabolism between walking and running at equivalent speeds during two incremental exercise tests.[Methods]Thirty four university students (18 males, 16 females) were recruited. Each participant completed two trials, consisting of walking (Walk) and running (Run) trials on different days, with 2-3 days apart. Exercise on a treadmill was started from initial stage of 3 min (3.0 k/m in Walk trial, 5.0 km/h in Run trial), and the speed for walking and running was progressively every minute by 0.5 km/h. The changes in metabolic variables, heart rate (HR), and rating of perceived exertion (RPE) during exercise were compared between the trials.[Results]Energy expenditure (EE) increased with speed in each trial. However, the Walk trial had a significantly higher EE than the Run trial at speeds exceeding 92 ± 2 % of the maximal walking speed (MWS, p < 0.01). Similarly, carbohydrate (CHO) oxidation was significantly higher in the Walk trial than in the Run trial at above 92 ± 2 %MWS in males (p < 0.001) and above 93 ± 1 %MWS in females (p < 0.05).[Conclusion]These findings suggest that EE and CHO oxidation during walking increase non-linearly with speed, and walking at a fast speed causes greater metabolic responses than running at the equivalent speed in young participants.

Metabolic function in patients with bipolar depression receiving anti-inflammatory agents: Findings from the MINDCARE study, a multicentre, randomised controlled trial

BackgroundMetabolic dysfunction is prevalent in bipolar disorder (BD) and associated with illness severity and treatment outcomes. There is little research exploring this relationship in low and middle-income countries (LMICs) and little is known about the moderating effect of metabolic health on treatment response to anti-inflammatory drugs in BD. MethodsMINDCARE, a randomized-controlled-trial conducted in Pakistan, investigated the efficacy of minocycline and celecoxib in 266 adults with bipolar depression. This secondary analysis evaluated the association between depression severity at baseline and treatment outcome with metabolic parameters including body mass index (BMI), waist circumference (WC), heart rate (HR), systolic blood pressure (s-BP), and diastolic blood pressure (d-BP). Depression severity was measured using the Hamilton Depression Rating Scale-17. The exploratory aim was to assess whether treatment impacted change in metabolic variables. Associations were evaluated using linear regression. ResultsHigher BMI (B=-0.38, 95%CI: -0.55 to -0.21) and WC (B=-0.68, 95%CI: -0.97 to -0.39) were associated with lower baseline depression severity in both the unadjusted and the adjusted models. Baseline metabolic parameters were not associated with treatment response to minocycline or celecoxib nor did treatment significantly impact metabolic variables. LimitationsOur sample represents patients in an RCT and may not be fully representative of the overall BD population in Pakistan. ConclusionsOur findings indicate a potential association of poor metabolic health and lower severity of bipolar depression but not treatment outcomes. Future work should evaluate potential relationships of metabolic parameters and BD in diverse populations to increase the transferability of this line of work.

Changes in Visceral Fat and Its Correlation With Changes in Metabolic Variables After Bariatric Surgery

Obesity is a health problem. There is a relationship between visceral adipose tissue (VAT) and various metabolic components. So far the most effective treatment for weight reduction and control of comorbidities is bariatric surgery. After bariatric surgery there is a reduction in VAT and a correlation with better control of metabolic variables would be expected. Objective: To determine the decrease in VAT, calculated by bioimpedance at 3 and 6 months after bariatric surgery and its correlation with changes in metabolic parameters (fasting glucose, HOMA, HbA1c, lipid profile). MATERIAL AND Methods: Patients belonging to the HECMNSXXI Obesity Clinic undergoing bariatric surgery during 2020 who agreed to participate in the study were included. VAT volume was determined before surgery and at 3 and 6 months after the procedure by bioimpedance using the SECA mBCA525 body analyzer. At the same time, biochemical metabolic markers were determined (fasting glucose, HOMA, HbA1c, CT, HDL, LDL, and triglycerides). The results were reported using descriptive statistics. A Pearson or Spearman correlation was carried out according to the distribution of the variables. P <0.05 was taken as significant. Results: Eleven patients with a mean age of 49 ± 7 years were included, 73% of them were women. Their average initial BMI was 42 ± 4 kg/m2. VAT prior to surgery had a mean of 10.6 ± 2.5L for men and 6.4 ± 2.4L for women. Eighty-two percent of the patients fulfilled harmonized criteria for metabolic syndrome. There was a statistically significant decrease in VAT at 3 and 6 months after surgery in both men and women (Baseline 7.5 ± 3L, 3 months 3.8 ± 2.8 L (p <0.001), 6 months 2.5 ± 2 L (p = 0.001). An average decrease in visceral adipose tissue of 57 ± 24% in women and 34 ± 18% in men (p = 0.18) was found 3 months after surgery and 70 ± 22% in women and 60 ± 21% in men (p = 0.53) 6 months after surgery. Laparoscopic one-anastomosis gastric bypass (OAGB) was the type of surgery with the highest percentage of VAT loss at 3 and 6 months, however, this was not statistically significant when compared with Y-Roux Gastric bypass (YRGB). A statistically significant decrease in HbA1c, HOMA, total cholesterol, LDL, and triglycerides levels were found at 3 and 6 months after surgery. However, when correlating the proportion of VAT lost with the metabolic variables, only a significant correlation was found with the HbA1c levels. The higher the proportion of VAT lost, the lower the HbA1c levels (R2 -0.72 p = 0.01). Conclusions: Bariatric surgery produces a statistically significant reduction in visceral adipose tissue from 3 months after surgery. In this study, an inversely proportional correlation was found between the proportion of VAT lost and HbA1c levels.

Performance determinants, running energetics and spatiotemporal gait parameters during a treadmill ultramarathon

PurposeThe objective of this study was to investigate the changes in metabolic variables, running energetics and spatiotemporal gait parameters during an 80.5 km treadmill ultramarathon and establish which key predictive variables best determine ultramarathon performance.MethodsTwelve participants (9 male and 3 female, age 34 ± 7 years, and maximal oxygen uptake (dot{V}O2max) 60.4 ± 5.8 ml·kg−1·min−1) completed an 80.5 km time trial on a motorised treadmill in the fastest possible time. Metabolic variables: oxygen consumption (dot{V}O2), carbon dioxide production (dot{V}CO2) and pulmonary ventilation (dot{V}E) were measured via indirect calorimetry every 16.1 km at a controlled speed of 8 km·h−1 and used to calculate respiratory exchange ratio (RER), the energy cost of running (Cr) and fractional utilisation of dot{V}O2max (F). Spatiotemporal gait parameters: stride length (SL) and cadence (SPM) were calculated via tri-axial accelerometery.ResultsTrial completion time was 09:00:18 ± 01:14:07 (hh:mm:ss). There were significant increases in dot{V}O2, Cr, F, dot{V}E and heart rate (HR) (p < 0.01); a significant decrease in RER (p < 0.01) and no change in SL and SPM (p > 0.05) across the measured timepoints. F and Cr accounted for 61% of the variance in elapsed finish time (R_{{{text{adj}}}}^{{2}} = 0.607, p < 0.01).ConclusionA treadmill ultramarathon elicits significant changes in metabolic variables, running energetics and spatiotemporal gait parameters. With F and Cr explaining 61% of variance in finish time. Therefore, those able to maintain a higher F, while adopting strategies to minimise an increase in Cr may be best placed to maximise ultramarathon performance.

Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial

Aims/hypothesisOral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome.MethodsA phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptible HLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory.ResultsRandomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by the INS genotype Among children with the type 1 diabetes-susceptible INS genotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%; p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes.Conclusions/interpretationThe study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptible INS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells.Trial registrationClinicaltrials.gov NCT02547519FundingThe main funding source was the German Center for Diabetes Research (DZD e.V.)Graphical abstract

Long-Term Assessment of Lurasidone in Schizophrenia: Post Hoc Analysis of a 12-Month, Double Blind, Active-Controlled Trial and 6-Month Open-Label Extension Study.

IntroductionA post hoc analysis of a double-blind (DB) active control trial and an open-label extension (OLE) study was conducted to evaluate the long-term effects of lurasidone in patients with schizophrenia.MethodsIn the DB trial, patients were randomised to receive lurasidone or risperidone for 12 months. In OLE, all patients received lurasidone for an additional 6 months. Treatment-emergent adverse events (TEAEs) were evaluated. Efficacy assessments included relapse rate (DB trial only), and Positive and Negative Syndrome Scale, Clinical Global Impression–Severity scale, and Montgomery–Åsberg Depression Rating Scale.ResultsIn the DB trial, patients with schizophrenia were randomised to lurasidone (n = 399) and risperidone (n = 190), of whom 129 and 84 continued into OLE, respectively. During the DB trial, incidence of TEAEs was similar for lurasidone (84.1%) and risperidone (84.2%). Lurasidone was associated with minimal changes in metabolic variables and prolactin levels, whereas risperidone was associated with clinically significant increases in prolactin and fasting glucose levels. The proportion of patients with metabolic syndrome was significantly lower in patients treated with lurasidone versus risperidone at the end of the DB trial (25.5% vs 40.4%; p = 0.0177). During OLE, patients switching from risperidone to lurasidone experienced a reduction in weight and prolactin levels; those continuing treatment with lurasidone experienced minimal changes in metabolic variables and prolactin. At the end of OLE, the proportion of patients with metabolic syndrome was no longer significantly different between groups (23.5% vs 31.5%; p = not significant). Efficacy outcomes were generally similar between groups during the DB trial, and were maintained during OLE.ConclusionLurasidone was generally well tolerated and effective in clinically stable schizophrenia patients over the long term. Lurasidone was also generally well tolerated and maintained effectiveness over 6 months in patients switching from risperidone. Patients switching from risperidone experienced improvements in metabolic parameters and prolactin levels. These findings confirm lurasidone’s long-term effectiveness and favourable metabolic profile in patients with schizophrenia.Trial RegistrationClinicalTrials.gov identifier NCT00641745.

Accuracy of a flash glucose monitoring system in dogs with diabetic ketoacidosis.

BackgroundA factory‐calibrated flash glucose monitoring system (FGMS; FreeStyle Libre) recently was evaluated in dogs with uncomplicated diabetes mellitus. It is not known if this system is reliable during diabetic ketoacidosis (DKA).ObjectivesTo assess the performance of the FGMS in dogs with DKA and to determine the effect of severity of ketosis and acidosis, lactate concentration, body condition score (BCS), and time wearing the sensor on the accuracy of the device.AnimalsFourteen client‐owned dogs with DKA.MethodsThe interstitial glucose (IG) measurements were compared with blood glucose (BG) measurements obtained using a validated portable glucometer. The influence of changes in metabolic variables (β‐hydroxybutyrate, pH, bicarbonate, and lactate) and the effect of BCS and time wearing on sensor performance were evaluated. Accuracy was determined by fulfillment of ISO15197:2013 criteria.ResultsMetabolic variables, BCS, and time wearing were not associated with the accuracy of the sensor. Good agreement between IG measurements and BG was obtained both before and after DKA resolution (r = .88 and r = .93, respectively). Analytical accuracy was not achieved, whereas clinical accuracy was demonstrated with 100% and 99.6% of results in zones A + B of the Parkes consensus error grid analysis before and after DKA resolution, respectively.Conclusions and Clinical ImportanceChanges in metabolic variables, BCS, and time wearing do not seem to affect agreement between IG and BG. Despite not fulfilling the ISO requirements, the FGMS provides clinically accurate estimates of BG in dogs with DKA.

Spontaneous ketonuria and risk of incident diabetes: a 12year prospective study.

Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic variables in a large population-based observational study. We analysed 8703 individuals free of diabetes at baseline enrolled in the Korean Genome and Epidemiology Study, a community-based 12year prospective study. Individuals with (n = 195) or without fasting ketonuria were matched 1:4 by propensity score. Incident diabetes was defined as fasting plasma glucose ≥7.0mmol/l, post-load 2h glucose ≥11.1mmol/l on biennial OGTTs, or current use of glucose-lowering medication. Using Cox regression models, HRs for developing diabetes associated with the presence of ketonuria at baseline were analysed. Over 12years, of the 925 participants in the propensity score-matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in participants with spontaneous ketonuria compared with those without ketonuria (HR 0.63; 95% CI 0.41, 0.97). Results were virtually identical when participants with fasting ketonuria were compared against all participants without ketonuria (after multivariate adjustment, HR 0.66; 95% CI 0.45, 0.96). During follow-up, participants with baseline ketonuria maintained lower post-load 1h and 2h glucose levels and a higher insulinogenic index despite comparable baseline values. The presence of spontaneous fasting ketonuria was significantly associated with a reduced risk of diabetes, independently of metabolic variables. Our findings suggest that spontaneous fasting ketonuria may have a potential preventive role in the development of diabetes.

Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers.

The sodium glucose co‐transporter‐2 inhibitor dapagliflozin has been shown to decrease urinary albumin‐to‐creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non‐response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non‐responders. At 24 weeks, the UACR‐adjusted mean change from baseline was −71.2% and 25.9% in responders and non‐responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non‐responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long‐term renal and cardiovascular outcomes remains to be determined.

Adiponectin promoter polymorphisms are predictors of lipid profile improvement after bariatric surgery.

Our aim was to investigate if single nucleotide polymorphisms (SNPs) located in the 5′ regions of leptin (LEP, -2548 G > A, rs7799039), resistin (RETN, -420 C > G, rs1862513) and adiponectin (ADIPOQ, -11391 G > A, rs17300539 and -11377 C > G, rs266729) genes were related to changes in body mass index (BMI) and metabolic variables after bariatric surgery in 60 extremely obese individuals. At baseline, ADIPOQ -11391 A-allele carriers showed higher plasma adiponectin and lower total cholesterol levels when compared to G/G homozygotes. Approximately 32 months post-surgery, a mean reduction of 35% in BMI and an important improvement in metabolic profiles were observed. In addition, for the ADIPOQ -11377 polymorphism, a higher decrease in lipid profile was associated to the C/C genotype. Moreover, individuals bearing the A-C haplotype for the two ADIPOQ SNPs were more prone to show a reduction in low-density lipoprotein levels after bariatric surgery (-43.0% A-C carriers vs. -18.1% G-G carriers, p = 0.019). We did not find any association of leptin and resistin SNPs with the clinical parameters analyzed. In summary, our results indicate that the A-C haplotype is a predictor of better lipid profile post-surgery and the studied SNPs in ADIPOQ gene are associated to changes in metabolic variables in obese individuals.

The use of metabolomics to monitor simultaneous changes in metabolic variables following supramaximal low volume high intensity exercise

High intensity exercise (HIE) stimulates greater physiological remodeling when compared to workload matched low-moderate intensity exercise. This study utilized an untargeted metabolomics approach to examine the metabolic perturbations that occur following two workload matched supramaximal low volume HIE trials. In a randomized order, 7 untrained males completed two exercise protocols separated by 1 week; (1) HIE150 %: 30 × 20 s cycling at 150 % VO2peak, 40 s passive rest; (2) HIE300 %: 30 × 10 s cycling at 300 % VO2peak, 50 s passive rest. Total exercise duration was 30 min for both trials. Blood samples were taken at rest, during and immediately following exercise and at 60 min post exercise. Gas chromatography-mass spectrometry analysis of plasma identified 43 known metabolites of which 3 demonstrated significant fold changes (HIE300 % compared to the HIE150 % value) during exercise, 14 post exercise and 23 at the end of the recovery period. Significant changes in plasma metabolites relating to lipid metabolism [fatty acids: dodecanoate (p = 0.042), hexadecanoate (p = 0.001), octadecanoate (p = 0.001)], total cholesterol (p = 0.001), and glycolysis [lactate (p = 0.018)] were observed following exercise and during the recovery period. The HIE300 % protocol elicited greater metabolic changes relating to lipid metabolism and glycolysis when compared to HIE150 % protocol. These changes were more pronounced throughout the recovery period rather than during the exercise bout itself. Data from the current study demonstrate the use of metabolomics to monitor intensity-dependent changes in multiple metabolic pathways following exercise. The small sample size indicates a need for further studies in a larger sample cohort to validate these findings.

Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor α blockers

ObjectivesTo evaluate prospectively the effect of weight loss on the achievement of minimal disease activity (MDA) in overweight/obese patients with psoriatic arthritis (PsA) starting treatment with tumour necrosis factor α...

OP0163 Weight loss and induction of minimal disease activity in psoriatic arthritis patients starting TNF-α blockers treatment

BackgroundPsA patients exhibit an increased prevalence of obesity. By leading to an abnormal expression of “adipokines” (TNF-α, IL-6, leptin, adiponectin), obesity determines a pro-inflammatory status. Thus, an interaction between obesity-related...

Calcium plus vitamin D3 supplementation facilitated Fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial

BackgroundRecent evidence suggests that higher calcium and/or vitamin D intake may be associated with lower body weight and better metabolic health. Due to contradictory findings from intervention trials, we investigated the effect of calcium plus vitamin D3 (calcium+D) supplementation on anthropometric and metabolic profiles during energy restriction in healthy, overweight and obese adults with very-low calcium consumption.MethodsFifty-three subjects were randomly assigned in an open-label, randomized controlled trial to receive either an energy-restricted diet (−500 kcal/d) supplemented with 600 mg elemental calcium and 125 IU vitamin D3 or energy restriction alone for 12 weeks. Repeated measurements of variance were performed to evaluate the differences between groups for changes in body weight, BMI, body composition, waist circumference, and blood pressures, as well as in plasma TG, TC, HDL, LDL, glucose and insulin concentrations.ResultsEighty-one percent of participants completed the trial (85% from the calcium + D group; 78% from the control group). A significantly greater decrease in fat mass loss was observed in the calcium + D group (−2.8±1.3 vs.-1.8±1.3 kg; P=0.02) than in the control group, although there was no significant difference in body weight change (P>0.05) between groups. The calcium + D group also exhibited greater decrease in visceral fat mass and visceral fat area (P<0.05 for both). No significant difference was detected for changes in metabolic variables (P>0.05).ConclusionCalcium plus vitamin D3 supplementation for 12 weeks augmented body fat and visceral fat loss in very-low calcium consumers during energy restriction.Trial registrationClinicalTrials.gov (NCT01447433, http://clinicaltrials.gov/).

Effect of weight loss, independent of change in diet composition, on apolipoprotein AI kinetic in men with metabolic syndrome

We investigated the effect of weight loss, independent of change in diet composition, on HDL and apoAI metabolism in men with metabolic syndrome (MetS). Subjects (19 men with MetS [NCEP-ATPIII]) were fed an isoenergetic Mediterranean-style diet for 5 weeks (all foods provided). Participants then underwent a 20-week free-living period during which they were counseled to restrict energy intake, after which they were again fed an isoenergetic Mediterranean-style diet for 5 weeks. At the end of the two controlled diets, participants received a single bolus of [5,5,5-(2)H(3)] (L)-leucine, and fasting blood samples were collected over a 96 h period. ApoAI kinetic was assessed using multicompartmental modeling of the tracer enrichment data. Participants achieved a 9.1 ± 2.8% reduction in body weight (P < 0.001). Weight loss resulted in an increase in plasma HDL-cholesterol (HDL-C) concentrations of 6.0% (P = 0.059) and HDL(3)-C of 7.9% (P = 0.045), attributable to a reduction in apoAI fractional catabolic rate (-7.8%; P = 0.046) with no change in apoAI production rate (2.2%; P = 0.58). These data indicate that weight loss, independent of variation in diet composition, increases plasma HDL primarily by delaying the catabolism of apoAI.

Weight Gain and Changes in Metabolic Variables following Olanzapine Treatment in Schizophrenia and Bipolar Disorder

Antipsychotic therapy forms the cornerstone of treatment for people with severe mental illness. Second-generation (atypical) antipsychotics are associated with a significantly lower incidence of extrapyramidal symptoms than the typical, first-generation agents; however, changes in metabolic variables -- including impaired glucose metabolism, diabetes mellitus, weight gain and dyslipidaemia -- have been reported during treatment with second-generation antipsychotics. Understanding any potential link between antipsychotic treatment and the incidence of these events is complicated by the increasing prevalence of obesity and diabetes occurring in the general population and the increased risk of diabetes and changes in metabolic variables in people with schizophrenia. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose level appears to fall on a continuum, with olanzapine appearing to have a greater association than some other atypical antipsychotics. The PubMed database was used to search for publications that included any information on measures of changes in weight, body mass index (BMI) and/or metabolic variables in randomized studies of olanzapine published between 1992 and 2010. In long-term (≥48 weeks) studies of olanzapine, the mean weight gain was 5.6 kg (last observation carried forward; median exposure 573 days). The proportions of patients who gained at least 7%, 15% or 25% of their baseline weight with long-term exposure were 64%, 32% and 12%, respectively. Some studies have suggested that weight gain early during the course of olanzapine treatment may predict clinically significant weight gain following long-term exposure to the drug. Changes in metabolic variables, such as elevated indices of glucose metabolism and triglyceride level, have also been observed during treatment with olanzapine. Consensus guidelines emphasize the importance of appropriate baseline screening and ongoing monitoring of weight gain and metabolic variables for people receiving all antipsychotic treatments. Long-term weight management programmes have been shown to reduce weight gain in some patients.

ORIGINAL ARTICLE: Metabolic outcome of GH treatment in prepubertal short children with and without classical GH deficiency

SummaryContext  Few studies have evaluated the metabolic outcomes of growth hormone (GH) treatment in idiopathic short stature (ISS). Moreover, children with ISS appear to need higher GH doses than children with GH deficiency (GHD) to achieve the same amount of growth and may therefore be at increased risk of adverse events during treatment. The individualized approach using prediction models for estimation of GH responsiveness, on the other hand, has the advantage of narrowing the range of growth response, avoiding too low or high GH doses.Design  Short prepubertal children with either isolated GHD (39) or ISS (89) participated in a 2‐year randomized trial of either individualized GH treatment with six different GH doses (range, 17–100 μg/kg/day) or a standard dose (43 μg/kg/day).Objective  To evaluate if individualized GH treatment reduced the variance of the metabolic measures as shown for growth response and to compare changes in metabolic variables in children with ISS and GHD.Hypothesis  Individualized GH dose reduces the range of metabolic outcomes, and metabolic outcomes are similar in children with ISS and GHD.Results  We observed a narrower variation for fasting insulin (−34·2%) and for homoeostasis model assessment (HOMA) (−38·9%) after 2 years of individualized GH treatment in comparison with standard GH dose treatment. Similar metabolic changes were seen in ISS and GHD. Delta (Δ) height SDS correlated with Δinsulin‐like growth factor I (IGF‐I), Δleptin and Δbody composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [Δlean body mass (LBM) SDS and ΔIGF‐I SDS] clustered together and correlated strongly with Δheight SDS and GH dose, whereas lipolytic variables [Δfat mass (FM) SDS and Δleptin] were clustered separately from anabolic variables. Regression analysis showed GH dose dependency in ISS, and to a lesser degree in GHD, for ΔLBM SDS and Δheight SDS, but not for changes in FM.Conclusions  Individualized GH dosing during catch‐up growth reduces the variance in insulin and HOMA and results in equal metabolic responses irrespective of the diagnosis of GHD or ISS.