Increased Fasting Plasma Glucose Levels Research Articles

Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice

Prediabetes is characterized by a cluster of glycemic parameters higher than normal but below the threshold of type 2 diabetes mellitus (T2DM). In recent years, phytochemical-rich plant extracts have gained popularity as therapeutic agents for metabolic disorders. This study investigated the effects of papaya leaf (PL) juice supplementation on blood glucose levels in diet-induced obese and prediabetic adult mice. B65JL F1 mice (n = 20) at 12–14 months old were fed a high fat/sugar diet (HFHS) for 120 days. Mice were switched to restricted rodent chow of 3 g feed/30 g body weight/day, supplemented with 3 g/100 mL PL juice for 30 days. HFHS diet remarkably increased fasting plasma glucose levels from 114 ± 6.54 mg/dL to 192.7 ± 10.1 mg/dL and body weight from 32.5 ± 1.6 to 50.3 ± 4.1 g. HFHS diet results in hyperglycemia, insulin resistance, hyperlipidemia, and liver steatosis. The combination of PL juice and restricted diet significantly reduced body weight and fasting blood glucose levels to 43.75 ± 1.4 g and 126.25 ± 3.2 mg/dl, respectively. Moreover, PL juice with a restricted diet significantly improved lipid profile: cholesterol from 204 to 150 mg/dL, LDL-c from 110.4 to 50 mg/dL, and triglyceride from 93.7 to 60 mg/dL. Additionally, PL juice combined with a restricted diet significantly reduced adiposity, reversed fatty liver, and restored skeletal muscle Glut4 and phosphorylated (p-AKT (ser473). This study demonstrated that supplementation of PL juice with a restricted diet was more effective than a restricted diet alone in reversing major symptoms related to prediabetic and obesity conditions.

Association of Dietary Patterns with Metabolic Syndrome among Middle-Aged Adults in Shiraz, Iran: Shiraz Heart Study (SHS).

Metabolic syndrome (MetS) is a noncommunicable disease with a high burden, including the development of type 2 diabetes mellitus, cardiovascular events, and death. It is characterized by abdominal obesity, elevated blood pressure, increased fasting plasma glucose levels, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol. MetS is preventable by modifying lifestyle and dietary patterns, which are major contributing factors. This research aimed to investigate the dietary patterns of the Shiraz Heart Study (SHS) and their associations with the occurrence of MetS and its components among middle-aged residents of Shiraz. Based on data from the Shiraz Heart Study (SHS), a prospective cohort study, the nutritional status of 1,675 participants was assessed using a food frequency questionnaire (FFQ). Three food patterns were extracted from the analysis named as vegan, western, and carbohydrate. Subjects were categorized into three levels for three major dietary patterns: low, moderate, and high, based on their adherence to each pattern. After adjusting the effect of co-founder variables, the relationship between dietary patterns, and the risk of developing MetS was analyzed. Of the 1,675 participants, 728 (43.5%) of them were male. The prevalence of MetS was 47.2%. Multivariate logistic regression analysis showed that high adherence to the vegan pattern was negatively associated with the occurrence of MetS (P value <0.001), while low adherence to the western pattern was also negatively associated (P value <0.05). Healthier diets, such as vegan diets, are significantly related to lower rates of MetS among the 40-70-year-old people in Shiraz, Iran.

Rare Heterozygous Loss-of-Function Variants in the Human GLP-1 Receptor Are Not Associated With Cardiometabolic Phenotypes.

Lost glucagon-like peptide 1 receptor (GLP-1R) function affects human physiology. This work aimed to identify coding nonsynonymous GLP1R variants in Danish individuals to link their in vitro phenotypes and clinical phenotypic associations. We sequenced GLP1R in 8642 Danish individuals with type 2 diabetes or normal glucose tolerance and examined the ability of nonsynonymous variants to bind GLP-1 and to signal in transfected cells via cyclic adenosine monophosphate (cAMP) formation and β-arrestin recruitment. We performed a cross-sectional study between the burden of loss-of-signaling (LoS) variants and cardiometabolic phenotypes in 2930 patients with type 2 diabetes and 5712 participants in a population-based cohort. Furthermore, we studied the association between cardiometabolic phenotypes and the burden of the LoS variants and 60 partly overlapping predicted loss-of-function (pLoF) GLP1R variants found in 330 566 unrelated White exome-sequenced participants in the UK Biobank cohort. We identified 36 nonsynonymous variants in GLP1R, of which 10 had a statistically significant loss in GLP-1-induced cAMP signaling compared to wild-type. However, no association was observed between the LoS variants and type 2 diabetes, although LoS variant carriers had a minor increased fasting plasma glucose level. Moreover, pLoF variants from the UK Biobank also did not reveal substantial cardiometabolic associations, despite a small effect on glycated hemoglobin A1c. Since no homozygous LoS nor pLoF variants were identified and heterozygous carriers had similar cardiometabolic phenotype as noncarriers, we conclude that GLP-1R may be of particular importance in human physiology, due to a potential evolutionary intolerance of harmful homozygous GLP1R variants.

Obesity modifies the association of environmental pyrethroid exposure with glucose homeostasis in the US general adults

Environmental pyrethroids are concerning due to their widespread residues and potential implications on human health. We aimed to assess the association of pyrethroid exposure with glucose homeostasis and examine the interaction between obesity and pyrethroid exposure. A total of 4233 US general adults from the National Health and Nutrition Examination Survey with measured urinary pyrethroid metabolites, fasting plasma glucose (FPG), fasting insulin (FINS), and glycated hemoglobin A1c (HbA1c) were included in the study. The homeostasis model assessment (HOMA2) calculator was utilized to assess insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS), and beta-cell function (HOMA2-β). We estimated the associations of pyrethroid metabolites with glucose homeostasis parameters (FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β) using multivariate linear regression models and restricted cubic spline models and further assessed the interaction between obesity and pyrethroid metabolites on glucose dyshomeostasis. Urinary 3-phenoxybenzoic acid (3-PBA) was the most detected pyrethroid metabolite (81%) with a median concentration of 0.43 (interquartile range 0.20–1.01) μg/g urinary creatinine. Compared with the participants in the lowest quartile, those in the highest quartile of 3-PBA had a 1.93% (95% confidence interval: 0.46%, 3.42%), 6.69% (1.96%, 11.64%), 1.60% (0.64%, 2.57%), 7.06% (2.33%, 12.01%), −6.59% (−10.72%, −2.28%), and 1.10% (−2.69%, 5.04%) alteration in FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β, respectively. The restricted cubic spline model displayed a linear positive association between 3-PBA and FPG, FINS, HbA1c, and HOMA2-IR, and a negative association with HOMA2-IS (all P for overall <0.05 and P for non-linear >0.05). Additionally, the association between urinary 3-PBA and FPG was modified by general obesity (P for interaction <0.05), with a more pronounced association observed in obese participants than in non-obese participants. Our findings suggested that pyrethroid exposure was associated with glucose dyshomeostasis. General obesity significantly heightened the association between pyrethroid exposure and increased FPG level.

Gestational Vitamin E Status and Gestational Diabetes Mellitus: A Retrospective Cohort Study.

To examine the association between vitamin E (VE) status and gestational diabetes mellitus (GDM). A retrospective cohort study was conducted by using data of 52,791 women at 137 hospitals across 22 provinces of China. A fasting plasma glucose (FPG) level of ≥5.1 mmol/L between the 24th and 40th weeks of gestation was used as the criteria for the diagnosis of GDM. Mean FPG level and GDM rate were calculated within each combination of the first-trimester VE concentration categories and gestational change categories. The associations of the first-trimester VE concentrations and gestational VE change with FPG and GDM were examined by employing generalized additive models (GAMs). 7162 (13.57%) cases were diagnosed with GDM. The GDM rate was 22.44%, 11.50%, 13.41%, 12.87%, 13.17%, 13.44%, 12.64%, and 14.24% among women with the first-trimester VE concentrations of <7.2, 7.2-7.9, 8.0-9.3, 9.4-11.0, 11.1-13.2, 13.3-15.8, 15.9-17.7, and 17.8-35.9 mg/L, respectively. The GDM rate was 15.96%, 13.10%, 13.64%, and 12.87% among women with gestational VE change of <0, 0-0.19, 0.20-0.29, ≥0.30 mg/L per week, respectively. Multivariable adjusted GAM analyses found that the first-trimester VE concentration was associated with the FPG levels and GDM risk in an L-shaped pattern; the FPG levels and GDM risk decreased sharply to a threshold (around 7 mg/L), and then were keep flat. Gestational VE decreases when the first-trimester VE level was less than 11 mg/L were related to increased FPG levels and GDM risk. Both low first-trimester VE levels and subsequent gestational VE decrease were related with increased risk of GDM. The findings suggest the necessity of having VE-rich foods and appropriate VE supplementation to prevent GDM for pregnant women with low baseline VE levels.

Changes in plasma IRAK-M in patients with prediabetes and its relationship with related metabolic indexes: a cross-sectional study.

ObjectiveTo investigate whether IL-1R-associated kinase (IRAK)-M is associated with prediabetes and type 2 diabetes (T2D).MethodsIn this cross-sectional study, enrolled subjects were assigned to different groups according to their fasting plasma glucose (FPG) values. IRAK-M and metabolic parameters, including fasting insulin (FINS), glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β), and thioredoxin-interacting protein (TXNIP), were evaluated. The area under the receiver operating characteristic curve of IRAK-M and TXNIP for prediabetes and T2D was determined.ResultsIRAK-M decreased significantly with increasing FPG levels. IRAK-M was negatively correlated with TXNIP, FPG, FINS, HbA1c, and HOMA-IR and positively correlated with HOMA-β. The diagnostic cutoff value of IRAK-M was 3.76 ng/mL for prediabetes and 3.45 ng/mL for T2D. After stratifying by IRAK-M (<3.76 and ≥3.76 ng/mL), patients with a higher TXNIP level showed a greater risk of prediabetes or T2D in the subgroup with low IRAK-M (<3.76 ng/mL).ConclusionsIRAK-M is independently and positively associated with prediabetes and T2D, while TXNIP is independently and negatively associated with prediabetes and T2D. IRAK-M and TXNIP serve as diagnostic factors for prediabetes.

Substantial PCSK9 inactivation in β-cells does not modify glucose homeostasis or insulin secretion in mice

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in cholesterol homeostasis by promoting the degradation of the LDL receptor (LDLR). PCSK9 loss-of-function mutations are associated with increased fasting plasma glucose levels and slightly elevated risk of type 2-diabetes. Considering the known detrimental effects of cholesterol accumulation in β-cell, and the widespread use of PCSK9 inhibitors to treat hypercholesterolemia, it is important to gain insight into the role of pancreatic PCSK9 in glucose homeostasis and β-cell function. We generated the first β-cell-specific KO of PCSK9 (βKO). PCSK9 mRNA and protein expression were reduced by 48% and 78% in βKO islets, respectively, indicating that β-cells constitute a major site of PCSK9 expression. In islets, loss of β-cell PCSK9 resulted in unchanged LDLR protein levels, but reduced LDLR mRNA, indicating that cholesterol internalization is enhanced and that β-cell PCSK9 promotes LDLR degradation. In contrast, whole body PCSK9 KO mice exhibited 2-fold higher LDLR protein levels in islets and a stable expression of cholesterogenic genes. Whole body KO and βKO mice presented normal glucose tolerance, insulin release in response to glucose load and insulin sensitivity. Ex vivo glucose-stimulated insulin secretion in presence or absence of fatty acids was similar in WT and KO islets. Like KO mice, individuals carrying loss-of-function PCSK9 variants may be protected from cholesterol-induced toxicity due to reduced circulating cholesterol levels. Using both whole body KO or βKO models, our data demonstrate that PCSK9 deletion in mouse does not have any toxic effect on β-cell function and glucose homeostasis.

Evaluation of the value of fasting plasma glucose in the first trimester for the prediction of adverse pregnancy outcomes

AimsTo evaluate the importance and usefulness of fasting plasma glucose (FPG) in the first trimester in predicting adverse pregnancy outcomes. MethodsA retrospective study of 22,398 singleton pregnancies was conducted. Participants were divided into subgroups according to first-trimester FPG (low FPG, FPG < 5.1 mmol/L; medium FPG, 5.1 mmol/L ≤ FPG < 5.6 mmol/L; high FPG, 5.6 ≤ FPG < 7.0 mmol/L) and oral glucose tolerance test(OGTT) results (normal and abnormal) during pregnancy. Patient characteristics and risk of adverse pregnancy outcomes were compared. Then, the whole population of women with abnormal OGTT served as a reference, and the relative risks of maternal and neonatal complications in normal OGTT women were analyzed by categorical analyses and logistic regression. Subgroup analyses were performed according to pre-pregnancy body mass index (BMI). ResultsThe frequency of adverse pregnancy outcomes increased with increasing FPG levels during the first trimester, regardless of OGTT results. High FPG + Abnormal OGTT had the worst outcome. Compared to the whole population of women with abnormal OGTT, Normal OGTT + Medium FPG showed the same risk of PIH and macrosomia. Normal OGTT + High FPG showed the same risk of PIH, macrosomia as well as LGA and preterm birth. Additionally, Normal OGTT + Medium FPG + BMI ≥ 24 kg/m2 showed significantly higher risk of PIH (OR = 1.867, 1.245–2.800), macrosomia (OR = 1.748, 1.304–2.344) and LGA (OR = 1.274, 1.019–1.593). Furthermore, the OR value for PIH was 3.759 (1.680–8.412) in Normal OGTT + High FPG + BMI ≥ 24 kg/m2 compared to women with abnormal OGTT. ConclusionsFirst-trimester FPG values can help identify women at increased risk for adverse pregnancy outcomes. Increased attention and management should be given to women with early pregnancy FPG ≥ 5.10 mmol/L despite a normal OGTT, especially if their BMI ≥ 24 kg/m2.

Improving Glucose Homeostasis after Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism with Co-Existing Prediabetes.

We have previously described increased fasting plasma glucose levels in patients with normocalcemic primary hyperparathyroidism (NPHPT) and co-existing prediabetes, compared to prediabetes per se. This study evaluated the effect of parathyroidectomy (PTx) (Group A), versus conservative follow-up (Group B), in a small cohort of patients with co-existing NPHPT and prediabetes. Sixteen patients were categorized in each group. Glycemic parameters (levels of fasting glucose (fGlu), glycosylated hemoglobin (HbA1c), and fasting insulin (fIns)), the homeostasis model assessment for estimating insulin secretion (HOMA-B) and resistance (HOMA-IR), and a 75-g oral glucose tolerance test were evaluated at baseline and after 32 weeks for both groups. Measurements at baseline were not significantly different between Groups A and B, respectively: fGlu (119.4 ± 2.8 vs. 118.2 ± 1.8 mg/dL, p = 0.451), HbA1c (5.84 ± 0.3 %vs. 5.86 ± 0.4%, p = 0.411), HOMA-IR (3.1 ± 1.2 vs. 2.9 ± 0.2, p = 0.213), HOMA-B (112.9 ± 31.8 vs. 116.9 ± 21.0%, p = 0.312), fIns (11.0 ± 2.3 vs. 12.8 ± 1.4 μIU/mL, p = 0.731), and 2-h post-load glucose concentrations (163.2 ± 3.2 vs. 167.2 ± 3.2 mg/dL, p = 0.371). fGlu levels demonstrated a positive correlation with PTH concentrations for both groups (Group A, rho = 0.374, p = 0.005, and Group B, rho = 0.359, p = 0.008). At the end of follow-up, Group A demonstrated significant improvements after PTx compared to the baseline: fGlu ((119.4 ± 2.8 vs. 111.2 ± 1.9 mg/dL, p = 0.021) (−8.2 ± 0.6 mg/dL)), and 2-h post-load glucose concentrations ((163.2 ± 3.2 vs. 144.4 ± 3.2 mg/dL, p = 0.041), (−18.8 ± 0.3 mg/dL)). For Group B, results demonstrated non-significant differences: fGlu ((118.2 ± 1.8 vs. 117.6 ± 2.3 mg/dL, p = 0.031), (−0.6 ± 0.2 mg/dL)), and 2-h post-load glucose concentrations ((167.2 ± 2.7 vs. 176.2 ± 3.2 mg/dL, p = 0.781), (+9.0 ± 0.8 mg/dL)). We conclude that PTx for individuals with NPHPT and prediabetes may improve their glucose homeostasis when compared with conservative follow-up, after 8 months of follow-up.

Associations of urinary carbon disulfide metabolite with oxidative stress, plasma glucose and risk of diabetes among urban adults in China.

Carbon disulfide (CS2) has been reported to induce disorder of glucose metabolism. However, the associations of CS2 exposure with plasma glucose levels and risk of diabetes have not been explored in general population, and the underlying mechanisms remain unclear. We aim to examine the relationships between CS2 exposure and fasting plasma glucose (FPG) levels, as well as diabetes, and assess the potential role of oxidative stress among the abovementioned relationships in Chinese general adults. The concentrations of urinary biomarkers of CS2 exposure (2-thiothiazolidin-4-carboxylic acid, TTCA), and biomarkers for lipid peroxidation (8-isoprostane, 8-iso-PGF2α) and DNA oxidative damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) were measured among 3338 urban adults from the Wuhan-Zhuhai cohort. Additionally, FPG levels were tested promptly. Generalized linear models and logistic regression models were used to quantify the associations among urinary TTCA, oxidative damage markers, FPG levels and diabetes risk. Mediation analysis was employed to estimate the role of oxidative damage markers in the association between urinary TTCA and FPG levels. We discovered a significant relationship between urinary TTCA and FPG levels with regression coefficient of 0.080 (95% CI: 0.002,0.157). Besides, the risk of diabetes was positively related to urinary TTCA (OR:1.282, 95% CI: 1.055,1.558), particularly among those who did not exercise regularly. Each 1% increase of urinary TTCA concentration was associated with a 0.096% and 0.037% increase in urinary 8-iso-PGF2α and 8-OHdG, respectively. Moreover, we found an upward trend of FPG level as urinary 8-iso-PGF2α gradually increased (Ptrend<0.05), and urinary 8-iso-PGF2α mediated 21.12% of the urinary TTCA-associated FPG increment. Our findings indicated that urinary CS2 metabolite was associated with increased FPG levels and diabetes risk in general population. Lipid peroxidation partly mediated the association of urinary CS2 metabolite with FPG levels.

Slightly Elevated Serum Ionic Fluoride Levels Inhibit Insulin Secretion and Increase Glucose Levels in a General Japanese Population: a Cross-sectional Study.

A cross-sectional study was performed to investigate the relationships between serum fluoride levels, glucose levels, and insulin secretion in a general population. A total of 330 healthy subjects (167 men; 163 women) aged between 40 and 69years were examined. Lifestyle information was obtained using questionnaires. Blood samples were collected in the early morning, and biochemical parameters and glucose indices were measured. Serum ionic fluoride (SIF) levels were assessed using a highly sensitive method. Relationships between glucose indices and SIF levels were investigated using a multiple linear regression analysis. SIF levels positively correlated with fasting plasma glucose (FPG) and glycohemoglobin (HbA1c) levels in both sexes. In women, SIF levels negatively correlated with homeostasis model assessment insulin secretion (HOMA-β) levels. In men, the proportion of regular drinkers negatively correlated with HOMA-β, but not SIF levels. Although SIF levels < 1μmol/L were associated with reduced insulin secretion and increased FPG levels, the risk of diabetes was not elevated. These results suggest that increased SIF levels caused by a large fluoride intake and compromised renal function combined with poor lifestyle choices elevate the risk of diabetes. Further studies are warranted to elucidate the effects of fluoride on glucose metabolism.

Long-term exposure to PM2.5 and fasting plasma glucose in non-diabetic adolescents in Yogyakarta, Indonesia

BackgroundIndonesia is facing serious air pollution. However, very few studies have been conducted to examine the health risks of air pollution in Indonesia, particularly for adolescents. ObjectiveTo assess the association between long-term exposure to ambient particles with a diameter of <2.5 μm (PM2.5) and fasting plasma glucose (FPG) in adolescents. MethodsA cross-sectional study was conducted in 482 adolescents aged 14–18 years in Yogyakarta, Indonesia in 2016. We finally included 469 (97.30%) participants who had no missing data for data analysis. We collected individual data on socio-demographics, behavioral habits, and health information through standardized questionnaires. Satellite-based PM2.5 concentrations from 2013 to 2016 were assigned based on participants’ residential addresses. The association between PM2.5 and FPG was examined using a generalized linear regression model while FPG was modeled as a continuous variable. An ordered logistic regression model was used to assess the relationship between PM2.5 and FPG categories. ResultsEvery 1 μg/m³ increase in PM2.5 was associated with a 0.34 mg/dL [95 confidence interval (95% CI): 0.08 mg/dL, 0.59 mg/dL] increase in FPG levels. Comparing with the low FPG level (under 86 mg/dL), every 1 μg/m³ increase in PM2.5 was associated with a 10.20% (95% CI: 1.60%, 19.80%) increase in the odds of impaired fasting glucose (IFG) (100–125 mg/dL). Stratified analyses indicated greater effects on participants with hypertension [odds ratio (OR) = 1.30, 95% CI: 1.09, 1.57] and those had higher physical activities (OR = 1.36, 95% CI: 1.09, 1.57). Adolescents’ sex, obesity status and different cutoff points of FPG did not modify the association between the exposure to PM2.5 and FPG levels. ConclusionLong-term exposure to PM2.5 was associated with increased FPG levels in Indonesian non-diabetic adolescents.

Relationship between fasting plasma glucose and incidence of diabetes in children and adolescents.

To investigate the appropriate fasting plasma glucose threshold by which to define prediabetes in children and adolescents, based on its ability to predict incident paediatric diabetes. In a nationwide survey of diabetes and renal disease conducted between 1992 and 2000 in all school-aged children in Taiwan, those with abnormal results in repeated urine tests received further physical examination and blood tests. Students who had blood tests for at least two time points were selected for the present study (N = 12 119). The incidence of paediatric diabetes, adjusted hazard ratio and predictive power of fasting plasma glucose were analysed. The incidence of paediatric diabetes increased with increasing fasting plasma glucose levels. Groups with fasting plasma glucose >5.6 mmol/l had a higher adjusted hazard ratio. The adjusted hazard ratio of incident diabetes for participants with higher fasting plasma glucose rose continuously when using a higher threshold for fasting plasma glucose. The area under the receiver-operating characteristic curve for fasting plasma glucose was 0.628 for predicting paediatric diabetes. The association between fasting plasma glucose and incident paediatric diabetes and the area under the receiver-operating characteristic curve were similar in boys and girls and were higher in the age group 12-18 years. According to receiver-operating characteristic curve analysis, the optimal thresholds, sensitivity and specificity were 4.75 mmol/l, 65% and 51%, respectively, for those aged 6-11 years and 5.19 mmol/l, 60% and 73%, respectively, for those aged 12-18 years. Fasting plasma glucose is associated with the incidence of paediatric diabetes. The results of the present study can be used as reference data to suggest a cut-off value to define paediatric prediabetes.

Type 2 Diabetes Mellitus: Integrative Analysis of Multiomics Data for Biomarker Discovery.

Increased fasting plasma glucose (FPG) is an independent risk factor for type 2 diabetes mellitus (T2DM). The development of systems biology technologies for integration of multiomics data is crucial for predicting increased FPG levels. In this case-control study, immunoglobulin (Ig) G glycosylation profiling and genome-wide association analyses were performed on 511 participants, and among them 76 had increased FPG (aged 47.6 ± 6.14 years), and 435 had decreased or fluctuant FPG (aged 47.9 ± 6.08 years). We identified nine single nucleotide polymorphisms (SNPs) in five genes (RPL7AP27, SNX30, SLC39A12, BACE2, and IGFL2) that were significantly associated with increased FPG (odds ratios 1.937-2.393). Moreover, of the 24 glycan peaks (GPs), GPs 3, 8, and 11 presented positive trends with increased FPG levels, whereas GPs 4 and 14 presented negative trends. A significant improvement of predictive power was observed when adding 24 IgG GPs to 9 SNPs with the area under the curve increased from 0.75 to 0.81. This report shows that the combination of candidate SNPs with IgG glycomics offers biomarker potentials for T2DM. The substantial predictive power obtained from integrating genomics and glycomics biomarkers suggests the feasibility of applying such multiomics strategies to enable predictive, preventive, and personalized medicine for T2DM.

Association of serum Fetuin-B with metabolic syndrome in obese Chinese adults

Objective To investigate the independent association of serum Fetuin-B with metabolic syndrome in obese Chinese adults. Methods Cross-sectional data on socio-demographic, lifestyle, clinical characteristics, and serum Fetuin-B were collected for 1 318 Chinese adults with central obesity. Associations of serum Fetuin-B with metabolic syndrome and insulin resistance were analyzed using multivariable Logistic regression analysis. Results A total of 820(62.2%)individuals were identified as metabolic syndrome. Subjects with metabolic syndrome showed significantly increased levels of serum Fetuin-B than those with non-metabolic syndrome [(4.18±1.39 vs 4.02±1.35)μg/ml, P=0.043]. Increased serum Fetuin-B were significantly associated with increased fasting plasma glucose and insulin levels, as well as prevalences of non-alcoholic fatty liver disease(NAFLD)and insulin resistance. After adjustment for potential confounders, serum Fetuin-B was significantly associated with increased risks of metabolic syndrome and insulin resistance(OR=1.19, 95%CI 1.06-1.34, P=0.004; OR=1.15, 95%CI 1.01-1.30, P=0.031 respectively). Conclusion Serum Fetuin-B level was significantly associated with NAFLD; and elevated serum Fetuin-B was significantly associated with increased risk of metabolic syndrome. (Chin J Endocrinol Metab, 2018, 34: 217-222) Key words: Fetuin-B; Non-alcoholic fatty liver disease; Metabolic syndrome; Insulin resistance; Cross-sectional study

Improvement of glucose metabolism via mung bean protein consumption: A clinical trial of GLUCODIATM isolated mung bean protein in Japan

Background: The main component of mung bean protein, accounting for more than 80%, is 8Sα globulin. Its structure closely resembles that of soybean β-conglycinin. Thereby, the mung bean protein is expected to have similar physiological effects to those of β-conglycinin, but there is no clinical evidence for these effects.Purpose of this study: The aim of this study was to confirm the positive effects of mung bean protein (GLUCODIATM) on glucose metabolism in clinical trials.Method: This clinical study was conducted using a double-blind placebo-controlled design with 45 prediabetes patients.Results: Many of the subjects were pre-diabetes with blood glucose levels exceeding 140 mg/dL by 2-hour plasma glucose level. However, the initial mean fasting plasma glucose level was less than 100 mg/dL. Therefore, mung bean protein did not lower fasting plasma glucose levels. The test period extended from summer to autumn, and increased fasting plasma glucose levels in the placebo group were observed due to seasonal factors. However, this increase was suppressed in the test group. Similarly, the mean insulin level increased in the placebo group, but the increase was also suppressed in the test group. Among obese subjects with a high body mass index, significant increases in fasting plasma glucose and insulin levels in the placebo group were observed. In the comparison between the test and the placebo groups with the average elevation value, there was a significant difference in fasting blood glucose level and significant tendencies in insulin level and homeostatic model assessment for insulin resistance value between the two groups.Conclusion: Mung bean protein suppresses fasting plasma glucose and insulin levels. Consequently, it may have an inhibitory effect on insulin resistance, a trigger of metabolic syndrome.Key words: mung bean protein, insulin, obesity, body mass index, randomized clinical trial, seasonal variation.

Ginsenoside Rg1 Inhibits Glucagon-Induced Hepatic Gluconeogenesis through Akt-FoxO1 Interaction.

Rationale: Glucagon is involved in hepatic gluconeogenesis, playing a key role in type 2 diabetes. Ginsenosides are reported to have antidiabetic activities. Ginsenoside Rg1 is a major propanaxatriol-type saponin in ginseng. This study aims to investigate the regulatory effects of Rg1 on glucagon-induced hepatic glucose production.Methods: The effects of Rg1 were investigated in high-fat-diet (HFD)-fed mice and glucagon-challenged C57BL/6J mice. Glucose metabolism was evaluated by oral glucose tolerance test and pyruvate tolerance test. The role of Rg1 on the regulation of Akt-FoxO1 interaction was performed using immunofluorescence, immunoprecipitation, siRNA silencing, pharmacological inhibitor and active-site mutant in primary hepatocytes or HepG2 cells.Results: Abnormally elevated fasting glucagon levels were observed in HFD-fed mice, contributing significantly to increased fasting plasma glucose levels. Inappropriate fasting glucagon secretion inactivated Akt and promoted hepatic glucose production via upregulation of FoxO1 activity. Rg1 preserved glucagon-impaired Akt activation partly by binding to Akt at Ser473 site. Rg1 also promoted Akt binding to FoxO1 and inactivated FoxO1 by phosphorylation. Consequently, Rg1 decreased the hepatic glucose production through a decrease in transcription of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). Both siRNA silencing of Akt and Akt inhibitor triciribine attenuated the effects of Rg1 in response to fasting hormone glucagon.Conclusion: Akt phosphorylation at Ser473 by ginsenoside Rg1 is critical for its gluconeogenesis-lowering effect, suggesting a potential for pharmaceutical intervention in response to fasting hormone glucagon.

Abstract 50: Procollagen C-endopeptidase Enhancer protein 2 (PCPE2) Deficiency Profoundly Affects Adipose Distribution in Mice and Humans and Links HDL Metabolism to Adipocyte Biology

Procollagen C-endopeptidase enhancer protein 2 (PCPE2) modulates selective HDL cholesterol ester uptake by SR-BI. Ldlr-/-,Pcpe2-/- mice develop greater aortic atherosclerosis despite increased concentrations of enlarged plasma HDL, suggesting PCPE2 confers functionality to HDL for reverse cholesterol transport. PCPE2 is a 52 kDa glycoprotein encoded by PCOLCE2 gene most highly expressed in adipose tissue, heart and aorta. PCPE2 has 2 CUB domains separated by a short linker, with each CUB domain containing a beta-sandwich fold, mediating a variety of protein-protein interactions. PCPE2 also contains a C-terminal netrin-like domain that binds tightly to cell surface glycosaminoglycans accounting for its location in the extracellular matrix. Because of the strong inverse correlation between HDL and triglyceride levels, and the potential role of SR-BI in triglyceride-rich lipoprotein uptake we examined Ldlr-/-,Pcpe2-/-mice fed a Western diet for 25 weeks. Ldlr-/-,Pcpe2-/- mice showed 1.7 fold increase in plasma triglyceride concentrations when compared to age and gender matched Ldlr-/- mice. We also noted that despite similar body weights, Ldlr-/-,Pcpe2-/- visceral fat pad weight was reduced 60% (p&lt;0.001, n=9 per genotype) compared to Ldlr-/- mice, while subcutaneous fat pad weight was not significantly different. This maldistribution of adipose in Ldlr-/-,Pcpe2-/- was associated with increased fasting plasma glucose levels, elevated 25% (p&lt;0.02) over Ldlr-/- mice. In humans, analyses showed significant correlations of subcutaneous fat PCPE2 RNA expression with DEXA traits from the TwinsUK cohort; % android fat (p&lt;0.0002), % trunk fat (p&lt;0.0001) and % gynoid fat (p&lt;0.04). Additional correlations between PCPE2 mRNA abundance and candidate marker expression will also be presented using 53 human visceral fat samples. Overall these data suggest that PCPE2 plays an important role in regional fat deposition linking SR-BI mediated cholesterol ester uptake to adipose cell biology.

Functional and genetic epidemiological characterisation of the FFAR4 (GPR120) p.R270H variant in the Danish population

Backgroundp.R270H (rs116454156) in the long chain fatty acid 7TM receptor FFAR4 (GPR120) which results in impaired Gαq (Gq) coupled signalling, has been associated with obesity. We aimed to extend the...

Angiotensin receptor blocker telmisartan suppresses renal gluconeogenesis during starvation.

The kidney plays an important role in gluconeogenesis during starvation. To clarify the anti-diabetic action of angiotensin receptor blockers, we examined the effects of telmisartan on the sodium-glucose co-transporters (SGLT) and the pathways of renal gluconeogenesis in streptozotocin-induced diabetes mellitus (DM) rats. At 4 weeks, the DM rats treated with/without telmisartan for 2 weeks and normal control rats were used for the study after a 24-hour fast. SGLT2 expressed on the brush border membrane of the proximal convoluted tubules increased in the DM rats, but decreased in the rats treated with telmisartan. The expression of restriction enzymes of gluconeogenesis, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased in the proximal tubules in the DM rats, whereas these enzymes decreased in the kidneys of the rats treated with telmisartan. The elevated cytoplasmic glucose-6-phosphate and glucose levels in the kidney of DM rats significantly decreased in those treated with telmisartan, whereas those levels in the liver did not show significant change. Meanwhile, the high plasma glucose levels in the DM rats during the intravenous insulin tolerance tests were ameliorated by telmisartan. The increased fasting plasma glucose levels after 24 hours of starvation in the DM rats thus returned to the control levels by telmisartan treatment. In conclusion, the increased renal SGLT2 expression, elevated renal gluconeogenesis enzymes and extent of insulin-resistance in the DM rats were ameliorated by telmisartan therapy, thus resulting in decreased plasma glucose levels after 24 hours of fasting.