Fasting Serum Research Articles

Comparison of Glucose and Immunoglobulin a Levels in Serum and Saliva of Patients with Type 1 and Type 2 Diabetes

Introduction: The monitoring and management of blood glucose levels are of significant importance in individuals diagnosed with diabetes mellitus. Accordingly, the objective of this study was to examine the potential of a non-invasive approach for the diagnosis and management of diabetes, through the measurement of glucose concentration and salivary IgA, and a comparison with fasting glucose and serum IgA levels in individuals with type 1 and 2 diabetes, in relation to a control group of healthy individuals. Methods: This case-control study was conducted on 76 individuals with diabetes (31 with type 1 diabetes and 45 with type 2 diabetes) and 24 healthy individuals. After obtaining the code of ethics and informed consent, serum and salivary IgA levels as well as fasting glucose, were measured for each participant. The data were analyzed using SPSS version 16 statistical software and the Spearman, Kruskal-Wallis, and Mann-Whitney tests. Results: The results showed a significant difference among the three groups (type 1 diabetes, type 2 diabetes, and healthy group) based on Fasting Blood Glucose, Hemoglobin A1c, Immunoglobulin A, salivary sugar, and salivary IgA (p<0.001). Additionally, in the case group, parameters such as FBS, HbA1c, and salivary IgA showed a significant correlation with salivary sugar. Conversely, in the control group, only the salivary sugar level demonstrated a significant relationship with serum glucose level. The study's findings indicated that serum and salivary IgA levels were lower and higher, respectively, in the control subjects compared to the diabetic group (p<0.001). Conclusion: In healthy individuals, salivary sugar can serve as an indicator to determine fasting blood sugar levels. In diabetic patients, salivary sugar can predict of FBS, HbA1c, and salivary IgA levels.

Assessment of glycemic control and correlation of HbA1c level with lipid profile and duration of diabetes in type 2 diabetes mellitus patients

Background & Objectives: The prevalence of Type 2 diabetes mellitus, or Type 2 DM, is rising globally. A periodic estimation of HbA1c has been recommended to track the state of glycemic control of Type 2 DM patients, in order to control the diabetes associated disorders. The main consequence and cause of death in Type 2 diabetes has been identified as cardiovascular disease (CVD).Optimization of glycemic status along with decreasing CVD risk factors are critical to preventing morbidity and mortality in patients with Type 2 DM. Since there is a lack of data on these CVD risk factors, in Madhesh Province, Nepal, we aimed to evaluate the glycemic status, estimate the lipid profile, and ascertain their correlation, including duration of Type 2 DM among patients in tertiary care hospitals in Madhesh Province, Nepal. Materials and Methods: The tertiary care hospital based cross-sectional study was conducted on 139 Type 2 DM patients, in Madhesh Province, Nepal. In order to gather information of the participants, a systematic questionnaire was introduced. A physical and clinical examination was performed, and an appropriate volume of blood was drawn with prior written consent. The lipid profile parameters, HbA1C, Fasting and post prandial serum glucose were estimated. Results: In 84 (60.3%) and 106 (76.3%) cases, there was an increased fasting and postprandial blood sugar. The mean±SD HbA1c level was 8.40±0.8%. More than half (52.5%) of the patients had poor glycemic control, while 22.3% had inadequate glycemic control, in reference to HbA1c >8% and 7 to 8%, respectively. A substantial increased level of LDL-C, triglycerides and total cholesterol was observed in 122 patients and 85.6% had reduced HDL-C. A significant strong positive association was found between HbA1c level and total cholesterol and triglycerides, in contrast, no discernible association with duration of disease observed. Conclusion: Glycemic control was inadequate. Triglycerides and total cholesterol were significantly positively correlated with HbA1c, but not with HDL-C, LDL-C, or the course of diabetes.

Association of Interleukin-6 gene (rs1800795) variant with waist-hip-ratio and Insulin resistance: A cross-sectional study in adult women

Obesity is a major contributing factor to metabolic disorders and public health problems worldwide. The goal of the current study was to determine if the Interleukin-6 gene rs1800795 variant is linked to waist-hip-ratio (WHR) and insulin resistance (IR) in North Indian adult women. The WHO guidelines were followed by 37 women who had a WHR >0.85 and 35 women who had a WHR <0.85, out of the 72 women who took part in the study. Every adult woman underwent anthropometric measures. Fasting blood glucose, serum Insulin, lipid levels, and IL-6 levels were measured, and IR was computed. The RFLP technique was used to polymorphise the IL-6 gene (174 G>C) variant. The study group's Insulin, HOMA-IR, BMI, lipid profile, TC/HDL ratio, HDL/LDL ratio, and serum IL-6 level were shown to differ significantly from the control. The percentage frequency of the IL-6 mutant genotype GC+CC (89.19%) and mutant allele C (75.68%) was higher in the study group (WHR >0.85). According to the findings, WHR, TC, TG, and HOMA-IR were substantially correlated (all p <0.05) with the mutant genotype GC+CC of the IL-6 174 G>C gene. This study indicates that the IL-6 rs1800795 gene (174 G>C) variant was substantially linked with metabolic risk variables, such as WHR and HOMA-IR.

Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis

Background:Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking.Methods:We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using two-sample Mendelian randomization and mice models.Results:Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7 and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2 hr glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice.Conclusions:Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes.Funding:South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes’ legat til forskning og bekjempelse av sukkersyke. The UK Biobank resource reference 53641. Australian National Health and Medical Research Council Investigator Grant (APP2017942). Australian Research Council Discovery Early Career Award (DE220101226). Research Council of Norway (Project grant: 325640 and Mobility grant: 287198). The Medical Student Research Program at the University of Oslo. Novo Nordisk Fonden Excellence Emerging Grant in Endocrinology and Metabolism 2023 (NNF23OC0082123).Clinical trial number:clinicaltrials.gov: NCT01803568.

The effects of spirulina (Arthrospira platensis) supplementation on serum fasting blood glucose, lipid parameters, and oxidative stress markers in male rats with type 2 diabetes

Background. Some studies have shown that Spirulina has biological properties exerting beneficial effects on human health. This study aimed to evaluate the effects of Spirulina supplementation on serum glucose, lipid parameters, and oxidative stress markers in male rats with streptozotocin/nicotinamide–induced T2DM. Methods. In this experimental study, rats with diabetes were divided into six groups: healthy control, diabetic control, diabetic-metformin, diabetic-Spirulina 100 mg/dL, diabetic-Spirulina 200 mg/dL, and healthy control-Spirulina 200 mg/d. At the end of the study (28 days), the blood samples were collected, and the fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined. Results. Significant reductions (P<0.001) were found in serum level of FBG in Metformin and Spirulina 100 mg/kg compared with diabetic control group. The groups were different regarding the serum levels of HDL-C post-intervention. ANOVA analysis also showed significant differences between the Spirulina 100 mg/kg or Metformin group and diabetic control group regarding the serum level of MDA (P<0.05). Conclusion. Spirulina at a dose of 100 mg/kg may have contributed to controlling the fasting blood glucose and oxidative stress. Practical Implications. Our study results suggested that Spirulina, as a promising agent, at lower doses may have been considered as a functional food for the management of diabetes mellitus.

Comparison of the Effectiveness of Single Anastomosis Sleeve Ileal Bypass and Roux-en-Y Gastric Bypass in Obese Patients with Type 2 Diabetes.

The rapid increase in obesity and related problems has heightened the importance of obesity and metabolic surgery, resulting in a continuing search for the ideal surgical method. This study aimed to compare the effectiveness of Roux-en-Y gastric bypass (RYGB), which is the gold standard method, and the relatively newer method of single anastomosis sleeve ileal (SASI) bypass. The medical records of patients who underwent RYGB and SASI bypass were reviewed and compared regarding excess weight loss (EWL) and HgA1c, fasting glucose, serum iron, ferritin, hemoglobin (Hgb), and vitamin B12 levels. The body mass index was significantly lower (p = 0.003), and the %EWL was significantly higher (p = 0.023) at 6months postoperative in patients who underwent SASI bypass. Both groups had similar results at the other follow-up visits. The mean HgA1c levels at the 6- and 12-month follow-up visits were significantly lower in SASI patients (p = 0.037 and p = 0.012, respectively). At the 24-month follow-up, no difference was detected in HgA1c levels between the groups (p = 0.476). In patients who underwent RYGB, ferritin (p < 0.001), plasma iron (p = 0.001), and Hgb levels (p = 0.001) were significantly lower at 12, 24, and 12months postoperatively, respectively. SASI bypass is effective and comparable to RYGB in terms of EWL and metabolic control and has the advantage of not producing excluded segments and reducing nutritional deficiencies.

Fasting hypertriglyceridemia in relation to mortality in an elderly male Chinese population.

We investigated fasting hypertriglyceridemia as predictors of all-cause, cardiovascular, and non-cardiovascular mortality in an elderly male Chinese population, while accounting for various conventional cardiovascular risk factors. Our participants were elderly men recruited from residents living in a suburban town of Shanghai (≥60 years of age, n=1583). Hypertriglyceridemia was defined as a fasting serum triglycerides concentration ≥1.70mmol/L. Subgroup analyses were performed according to current smoking (yes vs. no), alcohol intake (yes vs. no), and the presence and absence of hypertension and hyperglycemia. During a median of 7.9 years follow-up, all-cause, cardiovascular, and non-cardiovascular deaths occurred in 279, 112, and 167 participants, respectively. After adjustment for confounding factors, fasting hypertriglyceridemia was not significantly (p ≥.33) associated with the risk of all-cause, cardiovascular, and non-cardiovascular mortality. However, there was significant (p=.03) interaction between hypertriglyceridemia and the presence and absence of hypertension in relation to all-cause mortality. In normotensive, but not hypertensive individuals, hypertriglyceridemia was significantly associated with a higher risk of all-cause mortality (hazard ratio 1.57, 95% confidence interval 1.06-2.31). In further non-parametric analyses in normotensive individuals, the age-standardized rate for all-cause mortality increased from 18.9 in quartile 1 to 20.0, to 24.7, and to 39.9 per 1000 person-years in quartiles 2, 3, and 4 of serum triglycerides concentration, respectively (ptrend=.0004). Similar results were observed for cardiovascular mortality. Our study in elderly male Chinese showed that fasting hypertriglyceridemia was associated with a higher risk of all-cause and cardiovascular mortality in patients with normotension but not those with hypertension.

Comparison of fibroblast growth factor 19 concentrations between dogs with and without gallbladder mucoceles.

Fibroblast growth factor 19 (FGF19) is an enterohepatic hormone the synthesis of which is stimulated by bile acid activation of the nuclear farnesoid X receptor (FXR) in ileal enterocytes. Increased production of FGF19 downregulates hepatocyte bile acid synthesis and gluconeogenesis, while concurrently upregulating hepatocyte glycogenesis and gallbladder (GB) filling. The physiologic impact of this regulatory cycle is illustrated in cholecystectomized humans, in whom the disturbed meal-related flux of GB bile decreases serum FGF19 concentrations. Determine if serum FGF19 concentrations are lower in dogs with clinical GB mucoceles (GBMs) than in control dogs. Seven dogs with GBM diagnosed using abdominal ultrasonography, biochemical markers, and GB histopathology. Forty-two control dogs without gastrointestinal or hepatobiliary disorders also were evaluated. Health status of controls was assessed by physical examination and diagnostic hematologic and biochemical test results. Prospective cross-sectional study to compare fasting plasma or serum FGF19 concentrations between groups. Concentrations of FGF19 were quantified by a commercially available FGF19 ELISA. Concentrations of FGF19 were significantly lower in dogs with clinical GBM (median, 14.0 pg/mL; range, 12.8-67.2) than in control dogs (median, 145.3 pg/mL; range, 36.5-285.1). In dogs, GBM is associated with significantly decreased serum FGF19 concentrations. We speculate that this finding reflects compromised GB contraction and decreased enterohepatic circulation of bile flow. Subnormal FGF19 concentrations may influence bile acid synthesis and hepatic metabolism.

Biochemical study of the effect of lead exposure in nonobese gasoline station workers and risk of hyperglycemia: A retrospective case-control study.

Evaluate the relationship between blood lead (Pb) levels and other biomedical markers and the risk of diabetes in gasoline station workers. The participants were separated into 2 groups: group A consisted of 26 workers from gasoline filling stations, while group B comprised 26 healthy individuals. Serum levels of malondialdehyde, IL-1β, visfatin, insulin, fasting blood sugar, and vitamin D were assessed. Mean Pb level was significantly higher in group A compared to group B (almost 2.9 times higher levels) (14.43 ± 1.01 vs 5.01 ± 1.41, µg/dL). The levels of visfatin (23.19 ± 0.96 vs 3.88 ± 0.58, ng/mL), insulin (22.14 ± 1.31 vs 11.26 ± 0.75, mU/L), fasting blood sugar (118.4 ± 26.1 vs 82.7 ± 9.2, gm/dL), malondialdehyde (6.40 ± 0.27 vs 1.62 ± 0.21, nmol/mL), and IL-1β (330.25 ± 10.34 vs 12.35 ± 1.43, pg/mL) were significantly higher in group A, meanwhile; vitamin D (11.99 ± 1.55 vs 35.41 ± 3.16, ng/mL) were significantly lower in group A. A positive association exists between blood Pb levels and increased inflammatory markers. Lead exposure increases serum insulin and fasting blood sugar, which suggests that it is diabetogenic and that increased inflammation is a possible cause.

Dietary fatty acid pattern and its association with metabolic profile among overweight and obese adults

BackgroundNumerous studies have revealed the role of dietary fatty acids in human health. However, few studies have evaluated dietary fatty acid patterns and their association with metabolic parameters. The current study aimed to explore the association between dietary fatty acid patterns and risk factors for metabolic syndrome (MetS) among overweight and obese adults.MethodsThis cross-sectional study involved 340 participants who were overweight or obese. The study included assessments of body composition and anthropometric measurements. Dietary fatty acid consumption was evaluated using a validated Food Frequency Questionnaire (FFQ) containing 168 items. Additionally, biochemical parameters, including serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting serum glucose (FSG), and insulin levels, were measured using enzymatic methods. Fatty acid patterns were determined by principal component analysis (PCA), and the association between these dietary FA patterns and risk factors related to MetS components was assessed using logistic regression.ResultsFactor analysis conducted in this study explored three dietary fatty acid patterns: saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), and long-chain combined fatty acids (LC-CFA). Those at the highest tertile of the SFA pattern had lower diastolic blood pressure (DBP) (P = 0.03). Low-density lipoprotein cholesterol (LDL) was lower in the second and third tertiles (P ≤ 0.05). Also, higher fasting blood glucose (FBS) was observed in the second and third tertiles (P < 0.05), and the homeostatic model assessment of insulin resistance (HOMA-IR) was higher in the third tertile (P = 0.049). In the PUFA pattern, FBS was lower in the third tertile (P = 0.03). In the LC-CFA pattern, lower TC was achieved in higher tertiles (P = 0.04).ConclusionOur findings demonstrated that consuming high and moderate SFA patterns is associated with higher FBS and HOMA-IR. Also, increased consumption of SCFAs is related to lower DPB and LDL. Individuals who consumed more PUFA, especially linoleic acid, had lower FBS. These outcomes might be beneficial in managing MetS and leading to a new field of research.

The Effect of Conjugated Linoleic Acid Supplementation on Lipid-Related Cardiovascular Biomarkers in Obese Adults

Background: Studies have shown incompatible findings regarding the effects of conjugated linoleic acid (CLA) supplementation on cardiovascular diseases (CVDs) risk factors. The aim of this study was to evaluate the effect of daily CLA supplementation on serum insulin and lipid- related CV biomarkers in obese adults. Methods: This randomized double-blind clinical trial was conducted on 54 adults categorized as class I obesity. The participants were randomly assigned into two groups (n=27) receiving a total of 3,000 mg/d of a 50:50 mixture of CLA isomers for three months in intervention group (IG) and 500 mg/d paraffin in placebo group (PG). Moreover, fasting serum levels of insulin, lipid profile, non-HDL-Cholesterol (non-HDL-C), atherogenic index of plasma (AIP), total triglyceride (TG)/HDL-C, and cholesterol/HDL-C ratio were measured. The main statistical analysis method was independent t-test for changes. Results: Changes between the groups showed a significant decrease in total cholesterol (P=0.03), LDL-C (P=0.04), and non-HDL-C (P=0.03), and also a significant increase in AIP (P=0.04) in IG compared to the PG. A remarkable decrease was found in HDL-C and cholesterol/HDL-C ratio. In addition, a remarkable increase was observed in TG in this context. Serum insulin, VLDL-C, and LDL-C/HDL-C ratio showed no significant changes during the intervention period. The use of CLA supplementation could help reduce some adverse fractions of serum lipid profile, particularly TC, non-HDL-C and LDL-C. Conclusions: Regarding the augmenting effects of CLA intake on AIP as a strong predictive marker for CVDs, it is difficult to confirm the beneficial effects of CLA supplementation in preventing CVDs.

Testosterone with Silymarin Improves Diabetes-obesity Comorbidity Complications by Modulating Inflammatory Responses and CYP7A1/ACC Gene Expressions in Rats.

The co-morbidity of DMOB has become increasingly problematic among the world's population because of a high-calorie diet and sedentary lifestyle. DMOB is associated with lower testosterone (TN) levels, the male sex hormone. The phytochemical compound silymarin (SN) exerts antidiabetic activity by modifying β-cells and anti-obesity activity by inhibiting adipogenesis by methylxanthine. The goal of this study was to find out how well testosterone (TN) with silymarin (SN) protects against oxidative stress and inflammation in the liver of the experimental rats with type 2 diabetes (T2D) and obesity (DMOB). The present study evaluates the efficacy of TN and SN combination (TNSN) on the levels of the potential parameters, such as body mass, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profile, enzymatic and non-enzymatic antioxidants, proinflammatory cytokines, gene expression pathways, and histopathology in a DMOB comorbidity rat model. Male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 20 weeks with an administration of a single dose of streptozotocin (STZ) i.p. injection (30 mg/kg) on the 9th week of the study. The procedure was to develop the DMOB co-morbidity model in the experimental animals. Co-treatment of TN and SN administration were followed throughout the experiment. Rats were sacrificed after overnight fasting to collect serum and liver tissue samples. Samples were analyzed using a clinical chemistry automated analyzer, spectrophotometry, and quantitative real-time PCR (qPCR) methods and protocols. Analyses of body mass changes, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profiles, enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, adiponectin, CYP7A1, ACC expression pathways, and histopathology showed significant abnormal levels (P ≤ 0.05) in the pathological group. These were efficiently treated to normal by the administration of TNSN. These results concluded that TNSN exerted protective efficacy against the liver abnormalities in the co-morbidity of the DMOB rat model.

The effect of low-intensity suspension training with blood flow restriction on GH, IGF-1, and their association with physical fitness in young women.

Blood flow restriction (BFR) has been incorporated in resistance training for over 20 years. We aimed to investigate the impact of low-intensity suspension training with BFR (LIST+BFR) on GH, IGF-1, and their association with physical fitness in young women. Thirty-six active women participated and were randomly assigned to either the high-intensity suspension training (HIST), LIST+BFR, or control (CON) groups. Training groups exercised three sessions weekly for 8 weeks. The CON only engaged in regular physical activity. Fasting serum hormones and physical fitness were assessed 48 h before and after the training intervention. GH and IGF-1 levels significantly higher in the LIST+BFR compared to the HIST and CON. These hormones were significantly higher by HIST, compared to CON. LIST+BFR led to significant enhancements in muscular strength and endurance compared to HIST and CON. Additionally, HIST significantly higher than compared to CON. Sprinting and agility time lower in both suspension training groups rather than the CON. No significant between-groups differences were found in weight. There was a large or moderate correlation between GH and IGF-1 and muscular strength, endurance, sprint, and agility performance. LIST+BFR could more enhanced GH, IGF-1, and muscular strength and endurance in females than HIST.

Age- and Gender-Specific Reference Intervals for the Fasting Serum Lipid Levels in a Pediatric Population Aged 0-＜15 Years in Nanjing, China.

The lipid reference intervals (RIs) that are currently used for children in China are not based on studies of the local population and normally do not consider age or gender differences. This study aimed to establish age- and sex-specific RIs for the fasting serum lipid levels in the pediatric population aged 0 - 15 years in Nanjing, China. 5,866 children aged 3 days to ＜15 years were recruited to establish serum lipid RIs, and the triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed using the Roche cobas702 automatic biochemical analyzer. Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (nHDL-C) levels were calculated (LDL-C=TC-HDL-C-TG/5, and nHDL-C=TC-HDL-C). Smoothed percentile curves for the boys and girls were generated using the LMS method. Age- and sex-specific RIs were the determined according to the methods recommended by the Clinical and Laboratory Standards Institute EP28-A3c guidelines. This study showed that the serum lipid levels varied considerably throughout childhood and adolescence, with sex differences, especially in infants aged less than 2 years and puberty. Based on the Harris-Boyd method, sex partitions were required for ages ＜6 months in the TC indicator and for ages ≤ 28 days in LDL-C and nHDL-C. Age partitions were also required for all serum lipid parameters. We established age- and sex-specific RIs for TG, TC, HDL-C, LDL-C, and nHDL-C parameters in children aged 0 days to ＜15 years in Nanjing, China. These data are thus considered to be useful for the screening of dyslipidemia in children and adolescents.

Analysis of early-pregnancy metabolome in early- and late-onset gestational diabetes reveals distinct associations with maternal overweight.

It is not known whether the early-pregnancy metabolome differs in patients with early- vs late-onset gestational diabetes mellitus (GDM) stratified by maternal overweight. The aims of this study were to analyse correlations between early-pregnancy metabolites and maternal glycaemic and anthropometric characteristics, and to identify early-pregnancy metabolomic alterations that characterise lean women (BMI <25 kg/m2) and women with overweight (BMI ≥25 kg/m2) with early-onset GDM (E-GDM) or late-onset GDM (L-GDM). We performed a nested case-control study within the population-based prospective Early Diagnosis of Diabetes in Pregnancy cohort, comprising 210 participants with GDM (126 early-onset, 84 late-onset) and 209 normoglycaemic control participants matched according to maternal age, BMI class and primiparity. Maternal weight, height and waist circumference were measured at 8-14 weeks' gestation. A 2 h 75 g OGTT was performed at 12-16 weeks' gestation (OGTT1), and women with normal results underwent repeat testing at 24-28 weeks' gestation (OGTT2). Comprehensive metabolomic profiling of fasting serum samples, collected at OGTT1, was performed by untargeted ultra-HPLC-MS. Linear models were applied to study correlations between early-pregnancy metabolites and maternal glucose concentrations during OGTT1, fasting insulin, HOMA-IR, BMI and waist circumference. Early-pregnancy metabolomic features for GDM subtypes (participants stratified by maternal overweight and gestational timepoint at GDM onset) were studied using linear and multivariate models. The false discovery rate was controlled using the Benjamini-Hochberg method. In the total cohort (n=419), the clearest correlation patterns were observed between (1) maternal glucose concentrations and long-chain fatty acids and medium- and long-chain acylcarnitines; (2) maternal BMI and/or waist circumference and long-chain fatty acids, medium- and long-chain acylcarnitines, phospholipids, and aromatic and branched-chain amino acids; and (3) HOMA-IR and/or fasting insulin and L-tyrosine, certain long-chain fatty acids and phospholipids (q<0.001). Univariate analyses of GDM subtypes revealed significant differences (q<0.05) for seven non-glucose metabolites only in overweight women with E-GDM compared with control participants: linolenic acid, oleic acid, docosapentaenoic acid, docosatetraenoic acid and lysophosphatidylcholine 20:4/0:0 abundances were higher, whereas levels of specific phosphatidylcholines (P-16:0/18:2 and 15:0/18:2) were lower. However, multivariate analyses exploring the early-pregnancy metabolome of GDM subtypes showed differential clustering of acylcarnitines and long-chain fatty acids between normal-weight and overweight women with E- and L-GDM. GDM subtypes show distinct early-pregnancy metabolomic features that correlate with maternal glycaemic and anthropometric characteristics. The patterns identified suggest early-pregnancy disturbances of maternal lipid metabolism, with most alterations observed in overweight women with E-GDM. Our findings highlight the importance of maternal adiposity as the primary target for prevention and treatment.

Association of xanthine oxidoreductase inhibitor use with insulin secretory capacity in patients with type 2 diabetes.

Xanthine oxidoreductase (XOR) inhibitor treatment, which reduces reactive oxygen species (ROS) production and increases adenosine triphosphate (ATP) synthesis, has been reported to improve glycemic control. The possible protective effects of XOR inhibitor treatment on insulin secretory capacity were investigated in patients with type 2 diabetes. This retrospective cross-sectional study included 428 patients with type 2 diabetes. Insulin secretory capacity was assessed based on fasting serum C-peptide concentration (CPR) and C-peptide index (CPI) in all subjects, while insulin resistance in non-insulin users (n = 312) was determined using the homeostasis model assessment of insulin resistance (HOMA-IR) index. Median values for CPR and CPI in all subjects were 2.4 ng/mL and 1.5, respectively, while that for HOMA-IR in non-insulin users was 3.2. The XOR inhibitor users (n = 72) had significantly (P < 0.001) higher CPR and CPI levels than non-users (n = 356). Multivariable regression analyses showed XOR inhibitor use was positively associated with CPR (β = 0.153, P = 0.001) and CPI (β = 0.144, P = 0.001). Similar results were observed in propensity score analyses. In subgroup analyses of patients with a preserved estimated glomerular filtration rate (≥60 mL/min/1.73 m2) and non-insulin users, these associations remained significant. Furthermore, the associations were significant in patients with lower (≤6.0 mg/dL) but not with higher (>6.0 mg/dL) uric acid levels (P for interaction <0.05). On the other hand, XOR inhibitor use showed no significant association with HOMA-IR. The results of XOR inhibitor treatment, especially a sufficient reduction in serum uric acid level, may provide protective effects on insulin secretory capacity in patients with type 2 diabetes.

Associations between Adipose Tissue-Specific Insulin Resistance and Atherosclerotic Plaques and Burden in Community-Based Population.

We aimed to examine the association between adipose tissue-specific insulin resistance and atherosclerotic burden and plaques in intracranial, extracranial, and coronary arteries in community residents without diabetes. Adipose tissue-specific insulin resistance index (Adipo-IR) was calculated by fasting serum insulin and free fatty acids and categorized into 4 groups according to the quartiles. The 3.0 T magnetic resonance imaging scanner was used to assess intracranial and extracranial atherosclerotic plaques, while computed tomography angiography was used to assess coronary atherosclerotic plaques. Intracranial, extracranial, and coronary atherosclerotic burden was assessed by segmental stenosis segment scores of the corresponding arterial segments, respectively. Binary and ordinal logistic regression models were utilized to investigate the relationship of Adipo-IR with the presence of atherosclerotic plaques and atherosclerotic burden. Of 2,719 participants (mean [standard deviation] age, 60.9 [6.6] years; 1,441 [53.0%] women), the prevalence of intracranial atherosclerotic plaques, extracranial atherosclerotic plaques, and coronary plaques were 432 (15.9%), 975 (35.9%), and 1,160 (42.7%), respectively. Compared with individuals with the lowest quartile, participants with the fourth quartile of the Adipo-IR were associated with intracranial atherosclerotic burden (common odds ratio [cOR]: 1.35; 95% confidence interval [CI]: 0.99-1.82), coronary plaque (odds ratio [OR]: 1.45; 95% CI: 1.15-1.83), and segment stenosis score (cOR: 1.44; 95% CI: 1.15-1.81) after adjustment for age, sex, and current smoking. Adipose tissue-specific insulin resistance is associated with atherosclerotic burden and plaques in intracranial and coronary arteries in Chinese community nondiabetic residents.

Postprandial fatty acid-binding protein4 is associated with muscle insulin resistance.

Fatty acid-binding protein4 (FABP4) has been reported to act as a hepatic insulin resistance factor. We previously reported that fasting FABP4 was correlated with insulin resistance measurements derived from the glucose clamp, and another study reported that postprandial FABP4 levels were decreased in healthy volunteers but were not reported (or known) in participants with type 2 diabetes. We have limited knowledge about the direct effect of FABP4 on muscle cells. We investigated the postprandial FABP4 levels in participants with type 2 diabetes, and the basic mechanism of muscle insulin resistance and FABP4. We performed a meal tolerance test and hyperinsulinaemic-euglycaemic clamp in 22 participants with type 2 diabetes and 26 participants without diabetes. We measured fasting and postprandial serum FABP4. We cultured mouse C2C12 muscle cells, and investigated the effect of FABP4 on glucose uptake. We analysed insulin signalling by western blot and insulin binding assay. The postprandial FABP4 level in participants with type 2 diabetes was higher than that in participants without diabetes. Participants without diabetes had lower postprandial FABP4 than fasting except for one participant, whereas one-third of participants with type 2 diabetes had higher postprandial FABP4 than fasting. Postprandial FABP4 was correlated with the muscle insulin resistance M/I value from a glucose clamp in participants without diabetes (r=-0.42, p<0.05). The increase in FABP4 after a meal correlated with the muscle insulin resistance M/I value (r=-0.44, p<0.05) and the difference between fasting and postprandial glucagon in participants with type 2 diabetes (r=0.36, p<0.05). FABP4 alone appears to increase glucose uptake, and the combination of FABP4 and insulin decreases glucose uptake when compared with insulin alone. FABP4 inhibits insulin signalling of muscle cells through decreases in phosphorylation of insulin receptor substrate1 and Akt. The physiological concentration of FABP4 did not inhibit insulin binding to muscle cells. These results suggested that the postprandial FABP4 level is associated with insulin resistance, and FABP4 may suppress insulin signals.

Therapeutic role of Arabic gum against nicotinamide/streptozotocin-induced diabetes and nephropathy in Wistar rats

Background Chronic kidney disease is mainly caused by diabetic nephropathy and also causes a lot of suffering and death for people with diabetes, as one of the worst long-term complications. Arabic gum (AG) has been reported to have antioxidant, hypolipidemic and hypoglycemic effects. Objective The goal of this study was to scrutinize the antioxidant and anti-inflammatory roles of AG against nicotinamide (NA)/streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Materials and methods The experiment involved three groups of 18 adult male Wistar rats (six each). The normal control group received 0.9% NaCl orally for 8 weeks. The diabetic group received NA intraperitoneal injection (120 mg/kg b.w.) followed by 60 mg/kg body weight (bw) STZ in citrate buffer (pH 4.5) after 15 min. After confirming the induction of diabetes, animals received 0.9% NaCl orally for 8 weeks. The AG-treated diabetic group received 20 mg AG/kg bw/day orally for 8 weeks after diabetes induction. Results and conclusion Diabetic rats exhibited hyperglycemia which was confirmed by increased levels of serum fasting glucose and fructosamine. Elevated serum urea, creatinine, uric acid, cystatin c, and sodium levels were noticed in the serum of diabetic rats while potassium levels were markedly reduced reflecting nephropathy. Oxidative stress was evident in the diabetic kidney, as indicated by increased malondialdehyde (MDA) and decreased reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). AG administration ameliorated elevated fasting blood glucose and serum fructosamine levels as well as the kidney function parameters in serum. AG also attenuated oxidative stress and increased antioxidant capacity in the diabetic kidney. Immune-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and tumor suppressor protein (p53) expression were significantly upregulated in diabetic rats, but AG produced a downregulation of them. Thus, AG possesses an antidiabetic effect and has a nephropreventive effect that was manifested by a decrease of urea, creatinine, uric acid, cystatin c and sodium. AG also has anti-inflammatory and antioxidant effects and minimizes histopathological alterations in the kidneys of diabetic rats. Despite these ameliorative effects, the efficacy and safety of AG as an adjunct drug for diabetic kidney disease needs to be validated by more scientific research.

Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial

BackgroundWeight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism.MethodsPatients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8.ResultsSixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group.ConclusionsThese findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients.Trial registrationClinicalTrials.gov NCT03451734.