Impaired Fasting Glucose Patients Research Articles

Unraveling the pesticide-diabetes connection: A case-cohort study integrating Mendelian randomization analysis with a focus on physical activity's mitigating effect

Background and aimsThere is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. MethodsA total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. ResultsAfter 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. ConclusionsIndividual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.

From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures.

Background and aim-Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods-Thirty subjects, aged 45-65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results-Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions-The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations.

Hydrogen-Rich Water Ameliorates Metabolic Disorder via Modifying Gut Microbiota in Impaired Fasting Glucose Patients: A Randomized Controlled Study.

Molecular hydrogen (H2) exhibits antioxidant, anti-inflammatory and anti-apoptotic effects, and has shown benefits in glucose and lipid metabolism in certain animal metabolic disorder models. However, the potential benefits of H2 treatment in individuals with impaired fasting glucose (IFG) has seldom been studied. This randomized controlled study (RCT) aims to investigate the effects of hydrogen-rich water (HRW) on IFG subjects and explore the underlying mechanism involved. Seventy-three patients with IFG were enrolled in a randomized, double-blind, placebo-controlled clinical study. These patients were assigned to receive either 1000 mL per day of HRW or placebo pure water (no H2 infusion) for a duration of eight weeks. Metabolic parameters and fecal gut microbiota were assessed at baseline (week 0) and at week 8. A combined analysis of metabolomics and intestinal microbiota was conducted to investigate the correlation between the effect of H2 on the metabolisms and the diversity of intestinal flora in the IGF patients. Both pure water and HRW demonstrated a significant reduction in fasting blood glucose in IFG patients, with a significant difference between pure water and HRW after eight weeks. Among IFG patients with abnormal pre-experimental fatty liver, 62.5% (10/16) in the HRW group and 31.6% (6/19) in the pure water group achieved remission. Furthermore, 16S RNA analysis revealed HRW-modified gut microbiota dysbiosis in the fecal samples of IGF patients. Through Pearson correlation analysis, the differential gut microbiota obtained by 16S analysis was found to be highly correlated with nine metabolites. H2 slightly improved metabolic abnormalities and gut microbiota dysbiosis, providing a novel target and theoretical basis for the prevention and treatment of blood glucose regulation in patients with IFG.

Association between body mass index and reversion to normoglycemia from impaired fasting glucose among Chinese adults: a 5-year cohort study.

Evidence regarding the relationship between body mass index (BMI) and reversion to normoglycemia from prediabetes is still limited. The purpose of our study is to survey the link of BMI on reversion to normoglycemia among patients with impaired fasting glucose (IFG). This study, a retrospective cohort, covered 32 regions and 11 cities in China and collected 258,74 IFG patients who underwent a health check from 2010 to 2016. We investigated the association between baseline BMI and reversion to normoglycemia in patients with IFG using the Cox proportional-hazards regression model. The nonlinear relationship between BMI and reversion to normoglycemia was determined using a Cox proportional hazards regression with cubic spline functions and smooth curve fitting. In addition, we also performed a series of sensitivity analyses and subgroup analyses. A competing risk multivariate Cox regression was performed using progression to diabetes as a competing risk for reversal of normoglycemic events. After adjusting covariates, the results showed that BMI was negatively related to the probability of reversion to normoglycemia (HR=0.977, 95%CI:0.971-0.984). Compared with participants with normal BMI(<24kg/m2), overweight (BMI:24-28kg/m2) participants with IFG had a 9.9% lower probability of returning to normoglycemia (HR=0.901,95%CI:0.863-0.939), while obese patients (BMI ≥ 28kg/m2) had a 16.9% decreased probability of reverting from IFG to normoglycemia (HR=0.831,95%CI:0.780-0.886). There was also a nonlinear relationship between them, and the inflection point of BMI was 21.7kg/m2. The effect sizes (HR) on the left sides of the inflection point were 0.972(95%CI:0.964-0.980). The competing risks multivariate Cox's regression and sensitivity analysis demonstrated the robustness of our results. This study demonstrates a negative and nonlinear relationship between BMI and reversion to normoglycemia in Chinese patients with IFG. Minimizing BMI to 21.7 kg/m2 in patients with IFG through aggressive intervention may significantly increase the probability of returning to normoglycemia.

Angiogenic potential of plasma-derived extracellular vesicles from impaired fasting glucose patients: A pilot study

Angiogenic potential of plasma-derived extracellular vesicles from impaired fasting glucose patients: A pilot study

Extra Virgin Olive Oil Reduces Gut Permeability and Metabolic Endotoxemia in Diabetic Patients.

Background: Extra virgin olive oil (EVOO) improves post-prandial glycemia, but the underlying mechanism has not been fully elucidated. We tested the hypothesis that EVOO improves post-prandial glycemia by reducing gut permeability-derived low-grade endotoxemia. Methods: Serum levels of lipopolysaccharides (LPS), zonulin, a marker of gut permeability, glucose, insulin and glucagon-like peptide 1 (GLP1) were measured in 20 patients with impaired fasting glucose (IFG) and 20 healthy subjects (HS) matched for sex and age. The same variables were measured in IFG patients (n = 20) and HS (n = 20) before and after a Mediterranean diet with 10 g EVOO added or not (n = 20) or in IFG patients (n = 20) before and after intake of 40 g chocolate with EVOO added or not. Results: Compared to HS, IFG had higher levels of LPS and zonulin. In HS, meal intake was associated with a significant increase of blood glucose, insulin, and GLP1 with no changes of blood LPS and zonulin. Two hours after a meal intake containing EVOO, IFG patients showed a less significant increase of blood glucose, a more marked increase of blood insulin and GLP1 and a significant reduction of LPS and zonulin compared to IFG patients not given EVOO. Correlation analysis showed that LPS directly correlated with blood glucose and zonulin and inversely with blood insulin. Similar findings were detected in IFG patients given a chocolate added or without EVOO. Conclusion: Addition of EVOO to a Mediterranean diet or chocolate improves gut permeability and low-grade endotoxemia.

Prevalence of Impaired Fasting Glucose and Type 2 Diabetes in Kazakhstan: Findings From Large Study.

Type 2 diabetes mellitus (T2DM) is a serious public health problem. A large proportion of patients with T2DM are unaware of their condition. People with undiagnosed T2DM are at a greater risk of developing complications, whereas prediabetes has an elevated risk of becoming T2DM. The aim of this study is to estimate the prevalence of impaired fasting glucose (IFG), undiagnosed and prior-diagnosed T2DM in Kazakhstan. A cross-sectional study was conducted in four geographically remote regions using the WHO STEP survey instrument. The status of T2DM of 4,753 participants was determined using the WHO diagnostic criteria based on fasting plasma glucose (FPG) level. As a result, the survey-weighted prevalence of IFG was 1.9% (95% CI 1.1%; 3.5%) and of T2DM was 8.0% (95% CI 3.8; 15.9). A total of 54% of T2DM have been newly diagnosed with T2DM. Being 55–64 years old (OR = 2.71, 95% CI 1.12; 6.60) and having lowered HDL-C level (OR = 3.72, 95% CI 1.68; 8.23) were found to be independent predictors for IFG. Being older than 45 years, a female (OR = 0.57, 95% CI 0.39; 0.83), having high waist circumference, was associated with newly diagnosed T2DM. Whereas, the age older than 45 years, high waist circumference, and family history of diabetes (OR = 2.42, 95% CI 1.64; 3.54) were associated with preexisting T2DM. This study shows a high prevalence of IFG and a high proportion of newly diagnosed T2DM in Kazakhstan. A series of risk factors identified in the study may be used to strengthen appropriate identification of IFG or undiagnosed patients in healthcare settings to deliver either preventive or therapeutic interventions aimed to reduce the incidence of T2DM or the delay of their complications. Further longitudinal studies are needed to confirm these associations in our population.

The evaluation of intracellular energy metabolism in prediabetic patients and patients newly diagnosed with type 2 diabetes mellitus

Background/aimIncreased susceptibility to infections is a serious problem in diabetics. Impairment in the energy metabolism of the immune system is the main source of the problem. Early diagnosis of the impairment in energy metabolism is crucial. Our study aimed to investigate the energy metabolism in leukocytes in patient groups such as prediabetics and patients newly diagnosed with type 2 diabetes mellitus. Materials and methods Our study included 21 newly diagnosed type 2 diabetic patients (NDDP), 30 prediabetic patients, and 22 adult volunteers. 75 g oral glucose tolerance test (OGTT) was applied to all patients included in the study. Blood samples were taken after 9-16 h of fasting and fasting blood glucose (FBG), postprandial blood glucose (PBG) levels, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), fasting serum insulin, and hemoglobin A1c (HbA1c) levels were evaluated. After the cells were completely lysed, citrate levels from the released mononuclear leukocyte cells (MNC) content were manually studied, and lactate levels were applied to the autoanalyzer with the lactate kit. Lactate and citrate results were calculated as µg/mL. Statistical comparisons were done using Chi-square test, Mann-Whitney U test and student’s t test, and P < 0.05 values were accepted as significant. ResultsA significant difference was found between the controls and the other groups (newly diagnosed diabetic patients (NDDP), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT)) in terms of FBG levels (P < 0.001, P < 0.001 and P < 0.001, respectively). IFG and IGT patients had significantly higher PBG levels compared to the control group (P = 0.009 and P < 0.001, respectively). There was a significant difference between the IFG and IGT patients in terms of insulin levels (P = 0.019). There was a significant relationship between FBG levels and lactate production only in the NDDP group (r = 0.610, P = 0.003)ConclusionThe metabolic effects of hyperglycemia on leukocytes is in direction of anaerobic glycolysis. The increased anaerobic pathway is closely related to blood glucose levels and insulin resistance.

Considering serum alanine aminotransferase and gamma-glutamyltransferase levels together strengthen the prediction of impaired fasting glucose risk: a cross-sectional and longitudinal study

Emerging data suggest that an increase in serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as biomarkers of oxidative stress are associated with increased risk of impaired fasting glucose (IFG). The present study was an investigation of whether an increase in serum ALT and GGT had a combined effect on increasing IFG risk through cross-sectional and longitudinal studies. In the cross-sectional study, data were analyzed from 9937 subjects without diabetes who underwent health check-ups between 1999 and 2001 (baseline data). In the longitudinal study, 6390 subjects were analyzed who had been rechecked between 2009 and 2014, excluding IFG patients from baseline data. In cross-sectional analysis, adjusted odds ratio (OR) of IFG in the fourth quartile of both ALT and GGT was 1.829 (95% confidence interval [CI] 1.545–2.164) compared with the reference group (1st and 2nd quartiles of ALT and GGT). In longitudinal analysis, IFG probability increased gradually with an increase in the circulating levels of ALT and GGT. Adjusted hazard ratios for developing IFG in the fourth quartile of both ALT and GGT was 1.625 (95% CI 1.263–2.091) compared with the reference group (1st and 2nd quartiles). Increased serum ALT and GGT levels are well associated with IFG after potential confounders are adjusted for, and elevated ALT and GGT at the same time can have a combined effect in predicting the development of IFG.

Combination of Statin and Ezetimibe versus Statin Monotherapy on Cardiovascular Disease and Type 2 Diabetes Incidence among Adults with Impaired Fasting Glucose: a Propensity-Matched Nationwide Cohort Study.

ObjectiveWe investigated the effects of statin-ezetimibe combination therapy compared with statin-only treatment on the hazard of incident type 2 diabetes (T2D), myocardial infarction (MI), and stroke among adults with impaired fasting glucose (IFG) in a real-world setting.MethodsThe Korean National Health Insurance Service datasets from 2002 to 2017 were used for this propensity-matched nationwide cohort study. Among 56,633 IFG patients without baseline cardiovascular disease (CVD) and/or T2D who initiated statin therapy with or without ezetimibe, 1,155 with statin-ezetimibe combination therapy were matched based on a propensity score at a 1:5 ratio with 5,775 patients who received statin monotherapy. The hazards of T2D, MI, and stroke were compared between these treatment groups.ResultsThe incidence rate per 1,000 person-years was 19.62 (statin monotherapy group) and 21.02 (combined treatment group) for T2D, 1.53 (statin monotherapy group) and 1.70 (combined treatment group) for MI, and 1.99 (statin monotherapy group) and 2.06 (combined treatment group) for stroke. The hazards of T2D, MI, and stroke were not significantly different between the statin monotherapy group and the statin-ezetimibe combination therapy group.ConclusionThe combination of ezetimibe in addition to statin treatment was not associated with a significantly different risk of T2D and CVDs compared with statin monotherapy in Korean adults with IFG.

Incidence and risk factors of vascular complications in people with impaired fasting glucose: a national cohort study in Korea

This study aimed to evaluate the risk of vascular complications of impaired fasting glucose (IFG). This population-based study included 425,608 participants from the National Health Screening Cohort in Korea in 2003 and 2004 who were followed-up until 2015. The participants were classified into normal, IFG, and diabetes groups based on fasting plasma glucose levels. Incidence rate (per 1000 person-year) was evaluated for the following vascular complications: cardiovascular (ischemic heart disease, cerebrovascular disease, arterial and capillary disease), renal, and retinal diseases. Hazard ratios (HR) of IFG for diabetes were estimated after adjusting for patient characteristics. Among the 88,330 IFG participants, the incidence of cardiovascular, chronic renal and retinal diseases were 11.52, 0.47, and 1.08 per 1000 person-years, respectively. Furthermore, IFG patients with a family history of diabetes, past history of hypertension, and high body mass index had significantly increased risk of vascular complications [adjusted HR, cardiovascular: 1.39 (95% CI 1.33–1.46); renal: 2.17 (95% CI 1.66–2.83); and retinal: 1.14 (95% CI 0.98–1.32)]. IFG patients have a substantial risk of cardiovascular, chronic renal and retinal diseases. Therefore, early preventative interventions are beneficial, especially for those with high-risk factors, in whom should emphasize on maintaining a healthy lifestyle, early screening and continuous follow-up.

The Metabolic Effects of Cynara Supplementation in Overweight and Obese Class I Subjects with Newly Detected Impaired Fasting Glycemia: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Impaired fasting glucose (IFG) is a condition that precedes diabetes and increases the risk of developing it. Studies support the hypoglycemic effect of Cynara scolymus (Cs) extracts due to the content of chlorogenic acid, which is a potent inhibitor of glucose 6-phosphate translocase and of dicaffeoylquinic acid derivatives that modulate the activity of alpha-glucosidase. Given this background, we investigated whether a new highly standardized Cs extract could improve glycemic control, insulin sensitivity and other metabolic parameters (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) Triglycerides, Apolipo protein B (ApoB), Apolipo protein A (ApoA), waist circumference, visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) in overweight subjects with newly diagnosed IFG. Fifty-four subjects (females/males 26/28, mean ± SD age 51.5 ± 6.2) were randomly assigned to the supplemented group (n = 27) and placebo (n = 27). After multiple testing correction, statistically significant interactions between time and group were observed for the primary endpoint glycemia (β = 0.36, p < 0.0001) and for the secondary endpoints HDL (β = −0.10, p < 0.0001), total cholesterol/HDL (β = 0.27, p < 0.0001), LDL (β = 0.15, p = 0.005), LDL/HDL (β = 0.23, p = 0.001), insulin (β = 1.28, p = 0.04), glycated hemoglobin (β = 0.21, p = 0.0002), A1c-derived average glucose (β = 0.34, p = 0.0002), ApoB (β = 6.00, p = 0.01), ApoA (β = −4.50, p = 0.04), ApoB/ApoA (β = 0.08, p = 0.003), waist circumference (β = 1.89, p = 0.05), VATβ = 222.37, p = 0.005). In conclusion, these results confirm that Cs supplementation has a significant effect on metabolic parameters in IFG patients.

Association of Prediabetes and Type 2 Diabetes With Cognitive Function After Stroke

Background and Purpose- Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive performance in a stroke population. Methods- Seven international observational studies from the STROKOG (Stroke and Cognition) consortium (n=1601; mean age, 66.0 years; 70% Asian, 26% white, and 2.6% African American) were included. Fasting glucose level (FGL) during hospitalization was used to define 3 groups, T2D (FGL ≥7.0 mmol/L), impaired fasting glucose (FGL 6.1-6.9 mmol/L), and normal (FGL <6.1 mmol/L), and a history of diabetes mellitus and the use of a diabetes mellitus medication were also used to support a diagnosis of T2D. Domain and global cognition Z scores were derived from standardized neuropsychological test scores. The cross-sectional association between glucose status and cognitive performance at 3 to 6 months poststroke was examined using linear mixed models, adjusting for age, sex, education, stroke type, ethnicity, and vascular risk factors. Results- Patients with T2D had significantly poorer performance in global cognition (SD, -0.59 [95% CI, -0.82 to -0.36]; P<0.001) and in all domains compared with patients with normal FGL. There was no significant difference between impaired fasting glucose patients and those with normal FGL in global cognition (SD, -0.10 [95% CI, -0.45 to 0.24]; P=0.55) or in any cognitive domain. Conclusions- Diabetes mellitus, but not prediabetes, is associated with poorer cognitive performance in patients 3 to 6 months after stroke.

MON-LB50 Poor Response to Pre-Surgical Treatment With Somatostatin Receptor Ligands Is Associated With Diabetes Mellitus in Patients With Acromegaly

Introduction: somatostatin receptor ligands (SRL) represent the first-line medical therapy in acromegaly patients who were not cured by surgery and in those where surgical remission is unlikely. It is well known that SRL may negatively act on insulin secretion, with consequent hyperglycemia and diabetes mellitus (DM). Purpose: To evaluate whether the degree of response to surgical pre-treatment with SRL predicts alterations in blood glucose levels.Patients and Methods: We retrospectively studied 181 patients attending the Unit of Neurosurgery of our Hospital prior to transsphenoidal surgery. All patients had a biochemical and radiological diagnosis of acromegaly (nadir GH during OGTT >0.4 ng/mL; IGF-I above age-standardized UNL and pituitary adenoma at MRI scans); diagnosis of DM and impaired fasting glucose (IFG) was performed on fasting blood glucose (FBG) according to the American Diabetes Association guidelines; all parameters of the pituitary axes were determined. The response to SRL treatment was determined as percent change of GH levels. Data are presented as mean±SD; Continuous data normally distributed were analyzed using a two-tailed Student’s t-test to compare two groups, and one-way ANOVA to compare several groups, followed by the Bonferroni post-hoc procedure for pairwise comparison of groups after the null hypothesis was rejected (p<0.05); categorical data were analyzed by chi-squared test.Results: 97 (54%) patients with acromegaly underwent pre-surgical treatment with SRL; we found no difference in age (53±11 vs. 51±12 years; p=NS) and sex (M/F: 51/46 vs. 43/41; p=NS) between SRL treated and non-treated patients. We found no difference in FBG between SRL treated vs. non-treated patients. In contrast, we found increased proportions of IFG and DM patients in SRL treated when compared to non-treated patients (euglycemic: 45%, IFG: 42%, DM: 13% vs. euglycemic: 70%, IFG: 22%, DM: 8%, respectively; p=0.006). In addition, SRL treatment increased the odds ratio of IFG and DM (OR 4.7; 95%CI 2.1-10.3). When considering the degree of response to SRL pre-surgical treatment, we found that poor responders displayed at the time of surgery glycemias diagnostic of DM; whereas, good responders displayed glycemias in the range of IFG (percent change in GH levels 50±35% vs 79±22%, respectively; p<0.05).Conclusions: Our findings show that the proportion of patients with acromegaly undergoing surgery with glycemic levels diagnostic of DM, is modest. Interestingly, pre-treatment with SRL represents an independent risk factor for high glucose levels. Moreover, among patients on SRL pre-treatment, the ones that respond poorly are the ones that at the time of surgery display glycemias diagnostic of DM. Our findings suggest that SRL pre-treatment may predispose to worsened glucose metabolism but selectively affecting those patients in whom biochemical control is not reached.

Integrated biomarker for type 2 diabetes mellitus and impaired fasting glucose based on metabolomics analysis using ultra-high performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing but its early diagnosis in high risk populations remains challenging using only fasting blood glucose (FBG) or hemoglobin A1c measurements. It is, therefore, important to search for an integrated biomarker for early diagnosis by determining metabolites associated with the progression of the disease. We recruited 149 participants (51 T2DM patients, 50 individuals with impaired fasting glucose (IFG) and 48 normal glucose tolerance subjects). Their serum samples were analyzed based on a metabolomics approach using ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS). The changes in metabolites were profiled and evaluated using univariate and multivariate analyses. Furthermore, a biomarker model was established and the potential biomarkers were evaluated using binary logistic regression analysis and receiver operating characteristic analysis with AUC (area under the curve). Pathway analysis of differential metabolites was performed to reveal the important biological information. Thirty-eight differential metabolites were identified as significantly associated with T2DM patients and 23 differential metabolites with IFG individuals, mainly amino acids, carnitines, and phospholipids. By evaluating 17 potential biomarkers, we defined a novel integrated biomarker consisting of 2-acetolactate, 2-hydroxy-2,4-pentadienoate, L-arabinose and L-glutamine. The AUCs of the integrated biomarker with IFG and T2DM patients were 0.874 and 0.994, respectively, which showed a superior diagnostic performance. The levels of 2-acetolactate and 2-hydroxy-2,4-pentadienoate were strongly positively correlated with FBG, while L-glutamine and L-arabinose were strongly negatively associated with FBG. After pathway analysis, it was suggested that the majority of the influenced metabolic pathways associated with diabetes referred to amino acid metabolism. The integrated biomarker could diagnose IFG and T2DM with a superior diagnostic performance. This finding provides support for novel biomarkers in the diagnosis and treatment of diabetes.

Serum apelin-36 levels in pre-diabetics and newly diagnosed diabetes mellitus patients

Purpose: The aim of this study was to investigate the levels of parameters for glucose metabolism and cardiovascular risk factors and apelin-36 in patients grouped as having impaired fasting glucose(IFG), IFG and impaired glucose tolerance(IGT), newly diagnosed type 2 DM and the control group.Materials and Methods: Fifty-three women and twenty-seven men, totally eighty subjects were enrolled in this study. The patients were classified into four groups according to their oral glucose tolerance test (OGTT) results. Group1: Normoglycemic controls(n:20), Group2: subjects with IFG(n:20), Group3: combined IFG subjects which included both IFG and IGT patients(n:20), Group4: Newly diagnosed type 2 DM patients(n:20). Levels of glucose, lipids, HbA1c, fibrinogen, insulin, cortisol, serum apelin-36 and C-peptide were analyzed.Results: There was a statistically significant difference regarding the levels of apelin-36 between group 1 and the study groups 2, 3 and 4, respectively. Other parameters analyzed for glucose metabolism and cardiovascular risk factors such as fasting glucose, HbA1c, HOMA-IR, fibrinogen, insulin, cortisol, C-peptide, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, triglycerides, total cholesterol were significantly higher in the study groups when compared to the control group.Conclusion: In the future serum apelin-36 levels can be used as an indicator for presenting the insulin resistance and impairment in glucose metabolism in the early periods.

Risk factors analysis for developing diabetes based on its 3-year outcome in an elderly population with impaired fasting glucose

To examine the risk factors for developing diabetes on its 3-year outcome in an elderly population with impaired fasting glucose (IFG). We selected the 328 elderly with impaired fasting glucose in Binhai new area of Tianjin as the research object. All subjects participated in objective examinations such as physical activity ability tests, blood tests and anthropometric examinations, and completed the questionnaire survey. Between baseline and 3-year outcome, 56 of the subjects with IFG at baseline have developed diabetes. After multivariate adjustments, we found that higher incidence of diabetes was associated with higher fasting plasma glucose (OR=9.30, 95%CI 2.84-30.48, P<0.01) and reduced grip strength/weight (OR=0.88, 95%CI 0.82-0.94, P<0.01). Moreover, the combination of higher fasting plasma glucose and lower grip strength/weight would lead to higher incidence of diabetes compared with higher fasting plasma glucose or lower grip strength/weight alone (P<0.05). In this study, high fasting plasma glucose and low muscle strength were associated with blood glucose worsening in three years in IFG patients. In addition to blood glucose levels, physical activity is also a risk factor for diabetes in older adults. Key words: Impaired fasting glycaemia; Muscle strength; Elderly

Disposition Index in Active Acromegaly.

Background: The relative contribution of reduced insulin sensitivity (Si) or insulin secretion to impaired fasting glucose (IFG) or diabetes mellitus (DM) has not been clarified in active acromegaly. An intravenous glucose tolerance test (IVGTT) was never used for the calculation of Si, acute insulin response (AIRg), and disposition index (DI) in this population. Our aim was to assess Si, AIRg and DI using an IVGTT in acromegaly with normal (NGT) and abnormal glucose tolerance.Methods: We performed an IVGTT in 13 patients (8 NGT, 2 IFG, and 3 DM; 5 males, age 47.9 ± 11 years, body mass index 29.7 ± 4.1 kg/m2) with active acromegaly (insulin-like growth factor-1 4.1 ± 1.3 × upper limit of normal, basal GH 29.1 ± 25 ng/mL) and 3 healthy controls (2 males, age 39 ± 3 years, body mass index 23 ± 5 kg/m2). No patient had any growth hormone- or glucose-lowering medication.Results: NGT patients had significantly lower Si than healthy controls but higher AIRg. Hyperglycemic and normoglycemic patients had similar Si. DM patients had severely diminished AIRg (5–260 pmol × min/L) while IFG patients maintained their insulin secretion (3,862 and 912 pmol × min/L). Patients with abnormal glucose tolerance (IFG + DM) had a significantly lower DI (353 ± 350) than both NGT patients (3,685 ± 2,544) and healthy controls (5,837 ± 1,894; p < 0.01 for ANOVA).Conclusions: Disposition index suggests that although reduced insulin sensitivity is characteristic of active acromegaly it is the impaired insulin secretion that mainly drives glucose intolerance. The clinical utility of DI in predicting DM in acromegaly must be further investigated.

The Effect of Kelulut Honey on Fasting Blood Glucose and Metabolic Parameters in Patients with Impaired Fasting Glucose.

Background Impaired fasting glucose (IFG) poses a higher risk of diabetes. Honey has been reported to improve metabolic abnormalities including lowering hyperglycemia. This study is sought at determining the effect of Malaysian Kelulut honey (KH) on fasting glucose levels and metabolic parameters in IFG patients. Methods This quasi-experimental intervention study of 30-day duration was conducted among 60 adult patients with IFG. They were allocated into taking 30 g/day KH group (experimental group, n=30) and not taking KH group (control group, n=30). Body mass index (BMI), waist circumference, blood pressure (BP), fasting glucose, and lipid profile levels (total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein) were measured before and after treatment. Results There was no significant difference in all measured variables at day 30 compared to day 1 within both groups. Similarly, all measured variables neither at day 1 nor at day 30 had shown a statistically significant difference between the groups. Conclusions Daily intake of 30 g KH for 30 days resulted in insignificant effect on fasting glucose, fasting lipid profiles, and other metabolic parameters in patients with IFG. Further studies that employ longer study duration are needed to ascertain the finding.

Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.

Background and Aims Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C. Methods We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals. Results We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis. Conclusion We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.