Parameters Of Glucose Metabolism Research Articles

The Fabp4-Cre-Model is Insufficient to Study Hoxc9 Function in Adipose Tissue.

Developmental genes are important regulators of fat distribution and adipose tissue (AT) function. In humans, the expression of homeobox c9 (HOXC9) is significantly higher in subcutaneous compared to omental AT and correlates with body fat mass. To gain more mechanistic insights into the role of Hoxc9 in AT, we generated Fabp4-Cre-mediated Hoxc9 knockout mice (ATHoxc9-/-). Male and female ATHoxc9-/- mice were studied together with littermate controls both under chow diet (CD) and high-fat diet (HFD) conditions. Under HFD, only male ATHoxc9-/- mice gained less body weight and exhibited improved glucose tolerance. In both male and female mice, body weight, as well as the parameters of glucose metabolism and AT function were not significantly different between ATHoxc9-/- and littermate control CD fed mice. We found that crossing Hoxc9 floxed mice with Fabp4-Cre mice did not produce a biologically relevant ablation of Hoxc9 in AT. However, we hypothesized that even subtle reductions of the generally low AT Hoxc9 expression may cause the leaner and metabolically healthier phenotype of male HFD-challenged ATHoxc9-/- mice. Different models of in vitro adipogenesis revealed that Hoxc9 expression precedes the expression of Fabp4, suggesting that ablation of Hoxc9 expression in AT needs to be achieved by targeting earlier stages of AT development.

Crocin Improves Insulin Sensitivity and Ameliorates Adiposity by Regulating AMPK-CDK5-PPARγ Signaling.

Crocin is a carotenoid compound which possesses multiple biological activities. Our and other laboratory's previous findings show that crocin alleviates obesity and type 2 diabetes-related complications. We have found that crocin activates AMP-activated protein kinase (AMPK) signaling and inhibition of AMPK suppresses crocin-induced protective effects. However, the causal role of AMPK activation in the biological role of crocin is still not verified. In the present study, we showed that crocin markedly inhibits the changes of glucose metabolic parameters and serum lipid profiles in wild type diabetic mice. In AMPKα KO diabetic mice, those protective effects of crocin against glucose and lipid metabolic dysfunction were abolished. These results demonstrated AMPK activation was responsible for the beneficial effects of crocin on metabolic dysfunction. Moreover, we have shown that the antiobese effect of crocin has been abolished by the deficiency of AMPKα. We also showed that crocin induced a significant decrease of CDK5 protein level in wild type diabetic mice, while this effect was abolished in AMPKα KO diabetic mice. The regulation of downstream targets of CDK5/PPARγ by crocin was abolished by the deficiency of AMPK. In conclusion, our study verified that activation of AMPK is involved in crocin-induced protective effects against glucose and lipid metabolic dysfunction. Activation of AMPK downregulates the protein level of CDK5, followed by the decrease of PPARγ phosphorylation, leading to the inhibition of adipose formation and metabolic dysfunction. Our study provides new insights into the mechanism of protective effects of crocin and interaction of AMPK and CDK5/PPARγ signaling.

Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study

BackgroundUric acid (UA) is the end product of purine metabolism, which is thought to be related to many human diseases, such as nephrolithiasis, gout, cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome. However, the relationship between serum UA (SUA) and 25(OH) D is still unclear in the eastern Chinese population.MethodsWe did a population-based observational investigation, which included 12,770 residents living in eastern China. Ultimately, data from 9220 subjects were analyzed. Serum 25(OH) D, SUA, fasting plasma glucose (FPG), fasting insulin, HbA1c and other metabolic parameters were tested. Waist circumference (WC), weight and height were also measured. Questionnaires were collected from these subjects for information on smoking and drinking status.ResultsWe enrolled 9220 Chinese adults, including 3681 males (age 55.57 ± 13.23 years) and 5539 females (age 54.31 ± 12.83 years). The levels of SUA were 352.07 ± 79.25 nmol/L and 269.29 ± 64.68 nmol/L in males and females, respectively. The proportion of adults with hyperuricemia (HUA) was 12.26% in the total population. Levels of SUA were positively associated with 25(OH) D, and the incidence of HUA increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001).ConclusionsSUA was positively associated with 25(OH) D in the eastern Chinese population. Higher levels of serum 25(OH) D may be a potential predictor of HUA.

Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study.

We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions. Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded. Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein. VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance.

Do trends of adiposity and metabolic parameters vary in women with different ovarian reserve status? A population-based cohort study.

To investigate whether trends of adiposity and glucose metabolism parameters in women with low ovarian reserve status based on their anti-Mullerian hormone (AMH) levels differ from those with high ovarian reserve. In this population-based prospective study, eligible women, aged 20 to 50 years, were selected from among participants of the Tehran Lipid and Glucose Study (TLGS). Generalized estimating equation (GEE) models were applied to compare changes in various adiposity and metabolic parameters across time between women in the first and fourth quartiles of age-specific AMH, after adjustment for confounders. Pooled logistic regression was used to compare progression of prediabetes mellitus (pre-DM) and diabetes mellitus (DM) between the women of these two age-specific AMH quartiles. In this study of a total of 1,015 participants and with a median follow-up of 16 years, we observed that over time, both groups of women in the first and fourth quartiles of age-specific AMH experienced significant positive trends in their adiposity indices including central obesity, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and a negative trend in visceral adiposity index (VAI), whereas there was no significant difference in these parameters between the two groups. This study revealed that odds ratios of diabetes and prediabetes in women in the first quartile of age-specific AMH were not significantly different, compared with those in the fourth quartile. Women with lower ovarian reserve do not experience different over time trends of adiposity and glucose metabolism parameters during their reproductive life span.

2313-PUB: Alterations in Basal State of Insulin and mTOR-Dependent Signalings Closely Related to Impaired Incretin Profile and Type 2 Diabetes in Subcutaneous Adipose Tissue of Obese Patients

Objective: In our study we have compared basal insulin and mTOR signaling in subcutaneous fat of obese T2DM vs. obese subjects with normal glucose tolerance (NGT). We have performed correlation analysis of phosphorylation’s parameters against clinical parameters of carbohydrate metabolism and incretin secretion profiles. Methods: 22 patients with long (&amp;gt;10 years) and morbid (BMI &amp;gt; 35 kg/m2) obesity, 12 of which had NGT and 10 had T2DM were enrolled in this study. Hyperinsulinemic-euglycemic clamp test and HOMA-IR were used to measure insulin resistance. Blood samples taken at 0, 30 and 120 min of food load test were used to assess incretin profile, insulin and glucose levels. Amount of total and visceral fat was determined by bioelectrical impedance analysis. Subcutaneous fat biopsies were obtained during bariatric surgery for all patients and signaling state was analyzed by western blots. Results: As assessed by western blots of insulin receptor substrate (IRS), Akt, Raptor, Rictor, mTOR and S6K1, the basal insulin signaling and mTORC activities were comparable in NGT and T2DM groups, whereas phosphorylation of AS160 (pAS160-S318) was significantly lower and serum and glucocorticoid-induced kinase (SGK; pSGK-S422) was significantly higher in T2DM group. Various correlations were found between the degree of insulin resistance and amount of visceral fat, changes in incretin profile, glucose metabolic parameters and phosphorylation level of AS160, incretin secretion profile and phosphorylated levels of AS160 or SGK1. Conclusions: Altered phosphorylation of AS160 and SGK1 is associated with obese T2DM phenotype and impaired incretin profile. We think that AS160 and SGK1 phosphorylations can be important markers of the prediabetes-to-diabetes transition. Disclosure I. Stafeev: None. I. Sklyanik: None. S. Michurina: None. E. Shestakova: Employee; Spouse/Partner; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharma K.K., Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. A. Yurasov: None. K. Yahyaev: None. A. Karmadonov: None. E. Ratner: None. M. Menshikov: None. A.V. Vorotnikov: None. Y.V. Parfyonova: None. M.V. Shestakova: None. Funding Russian Science Foundation (17-15-01435)

Regional difference in the susceptibility of non-alcoholic fatty liver disease in China

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a global health problem with high geographic heterogeneity. We aimed to investigate regional-specific concomitant rate of NAFLD and quantitative relationship between liver fat content...

1862-P: Remission of Type 2 Diabetes and Metabolic Parameters Changes with a High-Protein Diet

The purpose of this study was to determine if remission of type 2 diabetes(T2D) can be achieved by macronutrients dietary changes without diabetes medications. High Protein (HP)(30% protein, 30% fat, 40% carbohydrates) or High Carbohydrate (HC)(15% protein, 30% fat, 55% carbohydrates) diets were used to study remission of type 2 diabetes(T2D) to Normal Glucose Tolerance(NGT), weight loss, body composition, and metabolic parameters in this randomized controlled clinical trial feeding study for 6 month(mo) in obese T2D adults. T2D adults age 20-65 years were randomized to a HP or HC diet for 6 mo with all food provided. Caloric need for weight loss was determined by Resting Metabolic Rate(RMR) -500 calories/day. Oral Glucose Tolerance Tests (OGTT) were performed at Baseline (BL) and 6 mo to determine T2D/NGT status. A BL ≥126 mg/dl and HbA1c ≥6.5% and 2 hr glucose &amp;gt;199mg/dl was considered T2D and remission was BL&amp;lt;126 mg/ml and HbA1c&amp;lt;6.5% and 2 hr glucose &amp;lt;140 mg/dl. DXA was done at BL and 6 mo. Food pick up and weight checks were weekly.The T2D subjects on HP diet had 100% remission to NGT while the HC diet subjects had 33% remission. Both diet groups had significant weight loss (HP =15.4±5 lb, HC=19.9±5 lb), improvement in insulin sensitivity determined by HOMA IR [HP(BL 5.3±0.29; 6 mo 2.1±0.13)], [HC(BL 5.2±0.27; 6 mo 4.4±0.26)] and decrease in HbA1c [HP(BL 7.7±.05; 6 mo 5.6±.02)], [HC(BL 7.8±.04; 6 mo 6.6±.06)] and blood pressure improvement S/D [HP (BL 129/85, 6 mo 117/78)], [HC(BL 130/85; 6 mo 117/78)]. HP group had a 2.7%± 0.4% increase in lean body mass and 2.9± 0.4% decrease in fat mass while the HC group had a 1.9%±0.3 and 3.3±0.9 % decrease in lean and fat mass respectively. Both diets resulted in weight loss, improvement in glucose tolerance and insulin sensitivity but only the HP diet produced 100% remission of T2D to NGT. Disclosure F.B. Stentz: None. A. Ammons: None. Funding AD Baskin (R073316012)

The Association of Potassium Status with Parameters of Glucose Metabolism is influenced by Age in Adults.

Potassium status has been found to affect glucose homeostasis. This study therefore aimed at investigating relationships between potassium status or dietary intake and fasting plasma glucose (FPG) or glycated haemoglobin (HbA1c) in a sample of Austrian adults (18-80 years, n = 421, 61% women) from the Austrian Study on Nutritional Status 2012. Dietary potassium intake was obtained by two 24 h recalls. FPG, plasma K+, and urinary K+ were determined photometrically, HbA1c by HPLC. Associations between the parameters were studied using multiple regression analysis after controlling for confounders and after age stratification of the sample (18-64 y vs. 65-80 y). Most of the participants had a potassium intake of less than the estimated adequate daily intake of 4000 mg/d. In the multiple regression analyses in the whole sample plasma K+ had a statistically significant positive effect on FPG only in the crude model (ß = 0.128, p < 0.01) and on HbA1c also in the fully adjusted model (ß = 0.129, p < 0.05). The small effects on HbA1c were also detected in the younger age group but were absent in the older population. However, in this latter, a reverse association of urinary K+ on HbA1c was observed as well as of dietary potassium intake on FPG with no effects in the younger sample. We suggest that age dependent differences in the association between parameters of potassium status and blood glucose regulation should also be taken into account.

Glycated Haemoglobin Is Associated With Poorer Cognitive Performance in Patients With Recent-Onset Psychosis.

BackgroundGlucose abnormalities and cognitive alterations are present before the onset of schizophrenia. We aimed to study whether glucose metabolism parameters are associated with cognitive functioning in recent-onset psychosis (ROP) patients while adjusting for hypothalamic-pituitary adrenal (HPA) axis measures.MethodsSixty ROP outpatients and 50 healthy subjects (HS) were studied. Cognitive function was assessed with the MATRICS Consensus Cognitive Battery. Glycated haemoglobin (HbA1c), glucose, insulin, and C-peptide levels were determined in plasma. The HOMA-insulin resistance index was calculated. Salivary samples were obtained at home on another day to assess the cortisol awakening response and cortisol levels during the day. Univariate analyses were conducted to explore the association between glucose metabolism parameters and cognitive tasks. For those parameters that were more clearly associated with the cognitive outcome, multiple linear regression analyses were conducted to adjust for covariates. Each cognitive task was considered the dependent variable. Covariates were age, sex, education level, diagnosis, antipsychotic and benzodiazepine treatment, body mass index (BMI), smoking, and HPA axis measures. Potential interactions between diagnosis and glucose parameters were tested.ResultsThere were no significant differences in HPA axis measures or glucose parameters, with the exception of C-peptide (that was higher in ROP patients), between groups. ROP patients had a lower performance than HS in all cognitive tasks (p < 0.01 for all tasks). Of all glucose metabolism parameters, HbA1c levels were more clearly associated with cognitive impairment in cognitive tasks dealing with executive functions and visual memory in both ROP patients and HS. Multivariate analyses found a significant negative association between HbA1c and cognitive functioning in five cognitive tasks dealing with executive functions, visual memory and attention/vigilance (a ROP diagnosis by HbA1c negative interaction was found in this latter cognitive domain, suggesting that HBA1c levels are associated with impaired attention only in ROP patients).ConclusionsOur study found that HbA1c was negatively associated with cognitive functioning in both ROP patients and HS in tasks dealing with executive functions and visual memory. In ROP patients, HbA1c was also associated with impaired attention. These results were independent of BMI and measures of HPA axis activity.

Prevalence of hyperuricaemia in an Eastern Chinese population: a cross-sectional study

ObjectivesIn the past decade, China has been characterised by large-scale urbanisation as well as rapid economic growth. The aim of this study was to further investigate the prevalence of hyperuricaemia...

Disorders of the glucose metabolism correlate with the phenotype and the severity in women with polycystic ovary syndrome

Different polycystic ovary syndrome (PCOS) phenotypes are correlated with different clinical severity levels. Insulin resistance correlates with higher severity. In a retrospective study, 130 patients with polycystic ovary syndrome were examined for insulin resistance. The aim of the study was to investigate relationships between glucose metabolism and different PCOS phenotypes and to identify biomarkers or combinations thereof to obtain information on the type of metabolic disorder or the severity of PCOS. A total of 130 patients with PCOS were included in the study. Biometric data such as weight, height, cycle day and cycle length were compared with glucose metabolism parameters such as fasting glucose, insulin before and 60 and 120minutes after 75g glucose intake, intact proinsulin, C-peptide and ovarian function parameters including Anti-Müllerian hormone (AMH) and the soluble AMH receptor (sAMHR2). The parameters were correlated, and their diagnostic performance with respect to different expressions of PCOS was evaluated. The biomarkers of impaired glucose metabolism showed strong significant difference in HOMA Index, adiponectin, proinsulin and body mass index (BMI) and Insulin levels in 0-60-120minutes of glucose tolerance test but also with parameters of ovarian function as AMH, AMH z-score sAMHR2, and sAMHR2/AMH ratio. A strong correlation between sAMHR2 and adiponectin (r=.818, P<.0001) was found indicating a relationship between the degree of glucose metabolic impairment and ovarian function. The parameters glucose, insulin, insulin 60minutes after intake of 75g glucose and adiponectin or sAMHR2 enable a biochemical classification of PCOS patients that correlates with morphological PCOS phenotypes. By determining biomarkers, it is possible to classify PCOS patients into subgroups that correlate with different PCOS phenotypes and the clinical severity.

Safflower Yellow and Its Main Component HSYA Alleviate Diet-Induced Obesity in Mice: Possible Involvement of the Increased Antioxidant Enzymes in Liver and Adipose Tissue.

PurposeOxidative stress plays an important role in the pathogenesis of obesity and its associated disorders. Safflower yellow (SY) and hydroxysafflor yellow A (HSYA), the natural compounds isolated from Carthamus tinctorius L., has been found to possess antioxidative and anti-obesity properties. The purpose of the present study is to investigate whether SY and its main component HSYA alleviate obesity by the antioxidant effects.MethodsDiet-induced obese (DIO) mice were treated with 200 mg/kg/d SY or HSYA for 10 weeks. Body weight, fat mass, serum biochemical parameters and superoxide dismutase (SOD) activities were measured. Glucose and insulin tolerance tests were performed. The expression of antioxidant enzymes in liver and adipose tissue were measured. In vitro, H2O2-induced oxidative stress HepG2 cells and 3T3-L1 adipocytes were treated with SY and HSYA to investigate the direct effects of SY and HSYA on the expression of antioxidant enzymes.ResultsSY and HSYA significantly decreased the body weight gain of DIO mice, and decreased fat mass to 57.8% and 61.6% of the control mice, respectively (P < 0.05). The parameters of glucose metabolism and liver function were improved after SY and HSYA treatment. The hepatic SOD activities and the mRNA levels of antioxidant enzymes in liver and adipose tissue of SY and HSYA treated mice were increased (P < 0.05). Meanwhile, the administration of SY and HSYA on the H2O2-induced oxidative stress HepG2 cells and adipocytes also increased the expression of the antioxidant factor and antioxidant enzymes to 1.2~3.3 folds of the control cells (P < 0.05).ConclusionSY and its main component HSYA could significantly decrease the fat mass, and improve glucose metabolism and liver function in diet-induced obese mice. The beneficial effects of SY and HSYA on obesity and metabolism may be associated with the increased expression of antioxidant enzymes in liver and adipose tissue.

Acute Effects of Three Different Meal Patterns on Postprandial Metabolism in Older Individuals with a Risk Phenotype for Cardiometabolic Diseases: A Randomized Controlled Crossover Trial.

The aim of this study is to investigate acute postprandial responses to intake of meals typical for Mediterranean and Western diets. In a randomized crossover design, overweight and obese participants with a risk phenotype for cardiometabolic diseases consumed three different isoenergetic meals: Western diet-like high-fat (WDHF), Western diet-like high-carbohydrate (WDHC), and Mediterranean diet (MED) meal. Blood samples are collected at fasting and 1, 2, 3, 4, 5h postprandially and analyzed for parameters of lipid and glucose metabolism, inflammation, oxidation, and antioxidant status. Compared to MED and WDHF meals, intake of a WDHC meal results in prolonged and elevated increases in glucose and insulin. Elevations for triglycerides are enhanced after the WDHF meal compared to the MED and the WDHC meal. Glucagon-like peptide-1 and interleukin-6 increase postprandially without meal differences. Apart from vitamin C showing an increase after the MED meal and a decrease after WDHF and WDHC meals, antioxidant markers decrease postprandially without meal differences. Plasma interleukin-1β is not affected by meal intake. Energy-rich meals induce hyperglycemia, hyperlipemia, an inflammatory response, and a decrease in antioxidant markers. A meal typical for the Mediterranean diet results in favorable effects on glycemic, insulinemic, and lipemic responses.

Zinc, copper, sirtuin 1 concentration, and glucose metabolism parameters in the blood of women with polycystic ovary syndrome

The aim of this study was to assess concentration of zinc (Zn), copper (Cu), and sirtuin 1 (SIRT1) in serum of women with polycystic ovary syndrome (PCOS) and their relationships with glucose metabolism parameters. The study included 76 women with PCOS aged between 17 and 39 years old. The blood was collected according to the routine procedure during the follicular phase. Zn and Cu concentrations were performed by flame atomic absorption spectrometry (FAAS). Glucose concentration was estimated by colorimetric methods. Insulin (INs) concentration was determined by enzyme-linked immunosorbent assay. SIRT1 concentration was determined using commercial test. We found higher Cu concentration and Cu/Zn value in the serum of women with PCOS with overweight/obesity. Early stage of insulin resistance (IR) in the group of women with PCOS affected on higher Cu concentration and Cu/Zn value. However, increased value of body mass index, waist-hip ratio and homeostatic model assessment of insulin resistance (HOMA-IR) was not associated with changes in Zn and SIRT1 concentration. Further disturbances in glucose metabolic parameters in the blood of women with PCOS were intensified by overweight/obesity and IR. Overweight/obesity and IR in the women with PCOS increase disorders in Cu homeostasis and glucose metabolism parameters.

Multiparametric positron emission tomography/magnetic resonance imaging in nasopharyngeal carcinoma: Correlations between magnetic resonance imaging functional parameters and 18F-fluorodeoxyglucose positron emission tomography imaging biomarkers and their predictive value for treatment failure.

Objectives:The clinical significance of positron emission tomography/magnetic resonance imaging (PET/MRI) functional parameters in nasopharyngealcarcinoma (NPC) remains unclear. The purpose of this prospective study was two-fold: (1) to investigate the associations between simultaneously acquired PET/MRI perfusion, diffusion, and glucose metabolism parameters in patients with NPC and (2) to analyze their predictive value with respect to treatment failure.Materials and Methods:We enrolled 85 patients with primary NPC who simultaneously underwent18F-fluorodeoxyglucose PET/CT and PET/MRI before definitive treatment. The following variables were determined: (1) functional parameters from the MRI component, including perfusion values (Ktrans,kep,ve, and initial area under the enhancement curve) and apparent diffusion coefficient (ADC) values, and (2) PET parameters, including metabolic tumor volume (MTV). The reciprocal interrelationships between these parameters and their correlations with treatment failure were examined.Results:We observed significant negative associations between Ktrans and ADC (r = −0.215, P = 0.049) as well as between ve and ADC (r = −0.22, P = 0.04). Correlations between PET and MRI functional parameters were not statistically significant. Treatment failures were observed in 21.2% of patients without distant metastases. Multivariate analysis identified ve as a significant independent predictor for treatment failure (P = 0.022), whereas MTV showed a borderline significance (P = 0.095). Patients in whom both ve and MTV values were increased had a significantly higher rate of treatment failure (62.5%) than those with either one (21.9%) or no (7.7%) increased parameter (P = 0.004).Conclusion:Correlation analyses revealed complex interrelationships among PET and MRI indices measured in patients with NPC. These parameters may have a complementary role in predicting treatment failure in this clinical setting.

Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents.

Background: Changes in the metabolic fingerprint of blood during child growth and development are a largely under-investigated area of research. The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of biospecimens for metabolomic analysis. The present study considered whether amino acid (AA) and acylcarnitine (AC) concentrations are associated with age, sex, body mass index (BMI), and puberty during childhood and adolescence. It also investigated whether there are associations between amino acids (AAs) and acylcarnitines (ACs) and laboratory parameters of glucose and lipid metabolism, as well as liver, kidney, and thyroid parameters. Methods: A total of 3989 dried whole blood samples collected from 2191 healthy participants, aged 3 months to 18 years, from the LIFE Child cohort (Leipzig, Germany) were analyzed using liquid chromatography tandem mass spectrometry to detect levels of 23 AAs, 6 ACs, and free carnitine (C0). Age- and sex-related percentiles were estimated for each metabolite. In addition, correlations between laboratory parameters and levels of the selected AAs and ACs were calculated using hierarchical models. Results: Four different age-dependent profile types were identified for AAs and ACs. Investigating the association with puberty, we mainly identified peak metabolite levels at Tanner stages 2 to 3 in girls and stages 3 to 5 in boys. Significant correlations were observed between BMI standard deviation score (BMI-SDS) and certain metabolites, among them, branched-chain (leucine/isoleucine, valine) and aromatic (phenylalanine, tyrosine) amino acids. Most of the metabolites correlated significantly with absolute concentrations of glucose, glycated hemoglobin (HbA1c), triglycerides, cystatin C (CysC), and creatinine. After age adjustment, significant correlations were observed between most metabolites and CysC, as well as HbA1c. Conclusions: During childhood, several AA and AC levels are related to age, sex, BMI, and puberty. Moreover, our data verified known associations but also revealed new correlations between AAs/ACs and specific key markers of metabolic function.

Association between brain glucose metabolism and cardiac dysfunction in patients with ischemic heart disease undergoing (18)F-FDG PET/CT imaging

Objective: To evaluate the relationship between the brain glucose metabolism and left ventricular function parameters, and to explore the cerebral glucose metabolism reduction regions in patients with ischemic heart disease (IHD). Methods: A total of 110 consecutive IHD patients who underwent gated (99)Tc(m)-sestamibi (MIBI) SPECT/CT myocardial perfusion imaging, gated (18)F-fluorodeoxyglucose (FDG) PET/CT myocardial and brain glucose metabolic imaging within three days in Beijing Anzhen Hospital from April 2016 to October 2017, were enrolled in this study. Left ventricular functional parameters of SPECT/CT and PET/CT including end-diastolic volume (EDV), end-systolic volume (ESV) and left ventricular ejection fraction (LVEF) were analyzed by QGS software. Viable myocardium and myocardial infarction region were determined by 17-segment and 5 score system, and the ratio of viable myocardium and scar myocardium was calculated. According to the range of viable myocardium, the patients were divided into viable myocardium<10% group (n=44), viable myocardium 10%-<20% group (n=36) and viable myocardium≥20% group (n=30). Pearson correlation analysis was used to analyze the correlation between the range of viable myocardium and scar myocardium and the level of cerebral glucose metabolism. Brain glucose metabolism determined by the mean of standardized uptake value (SUV(mean)) was analyzed by SPM. The ratio of SUV(mean) in whole brain and SUV(mean) in cerebellum were calculated, namely taget/background ratio (TBR). Differences in cerebral glucose metabolism among various groups were analyzed by SPM. Results: There were 101 males, and age was (57±10) years in this cohort. The extent of viable myocardium and the extent of scar, LVEF evaluated by SPECT/CT and PET/CT were significantly correlated with TBR (r=0.280, r=-0.329, r=0.188, r=0.215 respectively,all P<0.05). TBR value was significantly lower in viable myocardium<10% group, compared with viable myocardium 10%-<20% group (1.25±0.97 vs. 1.32±0.17, P<0.05) and viable myocardium≥20% group (1.25±0.97 vs. 1.34±0.16, P<0.05). Furthermore, in comparison with viable myocardium≥20% group, the hypo-metabolic regions of viable myocardium<10% group were located in the precuneus, frontal lobe, postcentral gyrus, parietal lobe, temporal lobe, and so on. Conclusions: There is a correlation between impaired left ventricular function and brain glucose metabolism in IHD patients. In IHD patients with low myocardial viability, the level of glucose metabolism in the whole brain is decreased, especially in the brain functional areas related to cognitive function.

Sitagliptin improves plasma apolipoprotein profile in type 2 diabetes: A randomized clinical trial of sitagliptin effect on lipid and glucose metabolism (SLIM) study

AimThis study aims to evaluate the effect of dipeptidyl peptidase-4 inhibitors on lipid metabolism in patients with type 2 diabetes mellitus (T2D). MethodsThis is a multicenter, open-labeled, randomized controlled study. T2D patients with HbA1c 6.9–8.9% (52–74 mmol/mol) who were under treatment with sulfonylurea were randomly allocated to either the sitagliptin group or the non-sitagliptin group. Glucose and lipid metabolism parameters including apolipoproteins (apo), sterols, and urinary albumin were assessed at baseline, 3, and 6 months of the treatment. ResultsA total of 164 patients completed the 6-month observation (n = 81 for sitagliptin and n = 83 for non-sitagliptin). HbA1c decreased in the sitagliptin group but not in the non-sitagliptin group. Serum TG and total, LDL and HDL cholesterol levels did not change in either group. Apo B-48, apo CII, and apo CIII levels decreased in the sitagliptin group, but not in the non-sitagliptin group. The change in urinary albumin was significantly different between the groups with a preferable change in the sitagliptin group. There were no changes in serum sterols levels in the two groups. ConclusionsThe treatment of sitagliptin for 6 months improves the metabolism of glucose and chylomicron and reduces plasma levels of atherogenic lipoproteins in patients with T2D.

Physical activity intervention for non-diabetic patients with non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials

BackgroundNon-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease nowadays. Changes in diet and lifestyle have led to a dramatic increase in the prevalence of NAFLD around the world. This meta-analysis is to investigate the efficacy of physical activity intervention on liver-specific endpoints in the population with NAFLD, including hepatic enzyme, serum lipid, glucose metabolism and intra-hepatic lipid.MethodsPubMed and China National Knowledge Infrastructure (CNKI) databases were searched for randomized clinical trials of physical activity intervention on NAFLD patients through April 20th, 2019. Effect sizes were reported as standardized mean difference (SMD) and 95% confidence intervals (CI). Quality of included studies was assessed according to the Cochrane risk of bias tool. Meta-analyses were conducted using random-effect or fixed-effect models depending on the significance of heterogeneity. Subgroup analyses according to types and duration of physical activity were conducted to investigate clinical variability.ResultsNine studies with a cumulative total of 951 participants met selection criteria. Physical activity was found associated with small reductions in hepatic enzyme parameters: ALT (SMD -0.17, 95% CI:-0.30 to − 0.05), AST (SMD -0.25, 95% CI: − 0.38, − 0.13) and GGT (SMD -0.22, 95% CI: − 0.36, − 0.08). Significant small improvements were also found in serum lipid parameters including TC (SMD = − 0.22, 95% CI: − 0.34, − 0.09), TG (SMD = − 0.18, 95% CI: − 0.31 to − 0.06) and LDL-C (SMD = − 0.26, 95% CI: − 0.39 to − 0.13). Significant improvement was also found in intra-hepatic lipid content (SMD = − 0.21, 95% CI: − 0.36 to − 0.06) There was no difference between physical intervention group and control group in HDL and three glucose metabolism parameters. Subgroup analysis suggested both aerobic exercise alone and resistance exercise alone can improve most liver function and longer period of exercise generally had better improvement effect.ConclusionsOur findings suggest that physical activity alone can only slightly improve hepatic enzyme levels, most serum lipid levels and intra-hepatic lipid content in non-diabetic patients with NAFLD.