Search

Purpose: The aim of this meta-analysis is to evaluate the role of Imeglimin in glycemic control (HbA1c & FPG), Homeostatic Model Assessment of β-cell function, pro-insulin to c-peptide ratio and its safety outcomes in patients with type 2 diabetes mellitus. Methods: A thorough literature search was performed on PubMed Central, PubMed, Cochrane, Wiley online library databases and efficacy outcomes such as changes in HbA1c, FPG, pro-insulin to c-peptide ratio and HOMA- β were summarized as standardized mean difference and safety outcomes were summarized as odds ratio. (PROSPERO registration no. CRD42023422787). Results: Seven randomized controlled trials conducted on 1,454 patients with type 2 diabetes mellitus were included. Overall the random effects model meta-analysis of standardized mean difference demonstrated that Imeglimin was significantly associated with HbA1c reduction of -0.85% (95% CI -1.08 to -0.62, p

Aims: The objective of the study was to compare screening performances of HbA1c, fasting plasma glucose (FPG), and two-hour plasma glucose (2hPG) in heart failure (HF) patients. Methods: We included 237 HF patients aged >20 years without history of diabetes, using National Health and Nutrition Examination Survey data (2005–2016). American Diabetes Association diabetes screening criteria were used: (1) HbA1c ≥6.5%, (2) FPG ≥126 mg/dL, and (3) 2hPG ≥200 mg/dL. Sensitivity, specificity, predictive values, and Receiver Operating Characteristic (ROC) curves for HbA1c and FPG were examined against reference methods. Results: N = 50 patients (20.5%) met at least 1 of 3 clinical criteria for diabetes. 2hPG alone identified 70.5% of patients, whereas HbA1c alone identified only 27.0% of patients. Sensitivity and specificity using a HbA1c cutoff at ≥6.5% were 24.4% and 97.6%, respectively. The Youden's J statistic for HbA1c was maximized at 6.1%. The area under the ROC curve of HbA1c against 2hPG was significantly lower compared to FPG (0.79, 95% CI 0.70-0.88; 0.89, 95% CI 0.84-0.94, respectively; p = 0.04). Conclusions: Blood glucose criteria are more sensitive than HbA1c when screening HF patients for diabetes. Future studies should test performance of a HbA1c cutoff at 6.1% when FPG or 2hPG cannot be completed.

Background: The impacts of long-term high exposure to PM2.5 in workplace on glucose metabolism in asymptomatic working adults (AWAs) have rarely been explored. Objectives: To assess the relationship between long-term exposure to workplace PM2.5 and glucose metabolism in asymptomatic general working adults in heavily polluted regions. Methods: We used the baseline data of the asymptomatic working participants from the Beijing-Tianjin-Hebei Medical Examination Cohort, which recruited adults undergoing medical examinations. A machine learning-based spatial–temporal model was used to estimate daily average PM2.5 concentrations in the participants’ workplaces. We assessed the association of long-term PM2.5 concentrations (three years prior to the interview) and fasting plasma glucose (FPG) using generalized linear mixed-effects models (GLMM) with inclusion of potential confounders. Stratified analyses by sex, age, BMI and smoking status, and two pollutant models were further performed. Results: A total of 37,619 individuals were interviewed and 28,865 were included in the analyses. The mean FPG was 5.20 (0.96) mmol/L, and the estimated three-year average concentration of PM2.5 exposure was 69.51 (6.92) μg/m3. We detected a significant association of long-term exposure to workplace PM2.5 and FPG, a 10 µg/m3 increase in the long-term workplace PM2.5 exposure was associated with 0.075 (95%CI: 0.050–0.100) mmol/L elevated FPG and 25% (OR = 1.25, 95%CI: 1.05–1.50) elevated odds of abnormal fasting glucose metabolism with control of the potential confounding. The detected association between workplace PM2.5 and FPG metabolism remained significant in males, individuals aged > 44 years, overweight and/or obese people, both smokers and non-smokers, and when NO2, SO2, O3, and CO were included in the model. Conclusions: Long-term exposure to workplace PM2.5 was associated with elevated FPG and/or odds of abnormal glucose metabolism among AWAs. Male, middle-aged, overweight and/or obese AWAs were more susceptible to workplace PM2.5 regardless of smoking status.

Background: The associations between the types/amounts of beverages consumed in daily life and measures of the glycemia status were investigated in a Japanese population-based cohort. Methods: Data from the baseline survey of the Japan Public Health Center-based Prospective Diabetes cohort were used. A cross-sectional analysis was performed in 3852 men and 6003 women who were evaluated under the fasting condition. The daily consumptions of coffee, green tea, oolong tea, black tea, soft drinks, fruit juices, or plain water were assessed using a self-reported questionnaire. Multivariable-adjusted linear regression analyses were performed using measures of the glycemia status (fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) ) as dependent variables and the types/amounts of beverages consumed as the independent variables, to calculate the differences according to the types/amounts of beverages consumed. Results: In the multivariable-adjusted models, coffee consumption of ≥240 mL/day was significantly associated with a change of the FPG level by −1.9 mg/dL in men (p = 0.013) and −1.4 mg/dL in women (p = 0.015), as compared to coffee consumption of 0 mL/day. No significant association of the FPG level was observed with any of the other types/amounts of beverages consumed. On the other hand, significant associations were found between the HbA1c levels and consumption of several types of beverages. Conclusions: High coffee consumption was associated with lower FPG levels in this Japanese population. Some unexpected associations of the HbA1c levels with the consumption of some types of beverages were observed, which need to be further investigated.

Summary: Background & aims: Vitamin D is being increasingly recognized for its important non-skeletal functions including endocrine actions. This study investigated if a single, large, intramuscular postpartum injection of vitamin D improve adiponectin levels among women with gestational diabetes mellitus (GDM). Methods: A total of 45 pregnant women with GDM participated in this randomized clinical trial. They were randomly divided into intervention and control group. The intervention group received an intramuscular injection of 300,000 IU of vitamin D during 3–10 days after their child delivery, but controls did not. Serum 25-hydroxyvitamin D, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and serum adiponectin were measured at baseline and after 3 months of intervention. Results: Serum 25 OH vitamin D increase significantly in the intervention but not in the control group from 24.25 to 62.10 (nmol/L) (p-value

Many metals are involved in the pathogenesis of diabetes, but most of existing studies focused on single metals. The study of mixtures represents real-life exposure scenarios and deserves attention. This study aimed to explore the potential relationship of urinary copper (Cu), zinc (Zn), arsenic (As), selenium (Se), and strontium (Sr) contents with fasting plasma glucose (FPG) levels in 2766 participants. The levels of metals in urine were determined by inductively coupled plasma–mass spectrometry. We used linear regression models and the Bayesian kernel machine regression (BKMR) to evaluate the association between metals and FPG levels. In the multiple metals linear regression, Zn (β = 0.434), Se (β = 0.172), and Sr (β = −0.143) showed significant association with FPG levels (all P

Background and Aims: Studies on the influence of fasting plasma glucose (FPG) on the development of carotid plaque (CP) and intima media thickness (CIMT) mainly focused on single FPG measures. We investigated whether changes in FPG (ΔFPG) are associated with incident CP and CIMT change (ΔCIMT) over time., Methods: Analyses were based on information from 1896 participants from the VIPVIZA trial (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention), with baseline and 3-year follow-up data on FPG, ultrasonographic CP (none or ≥1 lesion/s) and CIMT assessments. We studied the association between baseline FPG (prior to intervention) or 3-year ΔFPG (mmol/L) and incident CP (logistic regression) or ΔCIMT (linear regression). Analyses were adjusted for multiple potential confounders., Results: 1896 and 873 individuals, respectively, were included in the analysis on incident CP and ΔCIMT. Participants were 60 years old at baseline and 61% and 54% were females, in the CP and CIMT analyses, respectively. Every mmol/L increase in FPG was associated with an increased odds of incident CP (odds ratio: 1.42, 95% confidence interval [CI]: 1.17, 1.73), but there was no association with ΔCIMT (mean difference: 0.002 mm, 95% CI: -0.003, 0.008) after 3 years. Baseline FPG was not associated with incident CP nor ΔCIMT progression., Conclusions: In middle-aged individuals with low to moderate risk for cardiovascular diseases, 3-year ΔFPG was positively associated with the risk of incident CP, but not with ΔCIMT. Single measures of FPG may not be sufficient in estimating cardiovascular risk among individuals with low to moderate risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Associations between per- and polyfluoroalkyl substances (PFASs) and the incidence of type 2 diabetes are controversial in epidemiological studies. In addition, limited data are available for assessing the health effects of novel PFAS alternatives. Our study evaluated the effects of PFAS exposure on type 2 diabetes by estimating the associations of PFASs in human serum with the risk of type 2 diabetes and levels of glycemic biomarkers and lipid fractions. The case-control study consisted of 304 participants from Shandong Province, East China, half of which were diagnosed with type 2 diabetes. Logistic regression showed that most PFASs were inversely associated with the risk of type 2 diabetes after adjusting for age, sex, and body mass index. However, concentrations of perfluorooctanoic acid (PFOA) in the control group were positively associated with fasting plasma glucose levels (β = 0.04, 95% confidence interval (CI): 0.0003, 0.08), which may promote the development of type 2 diabetes. Furthermore, each log-unit increase in the concentrations of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (Cl-PFESA) were associated with a total cholesterol increase (i.e., 17.49% (95% CI: 0.93%, 34.90%), 17.49% (95% CI: 4.71%, 31.83%), and 17.49% (95% CI: 4.71%, 31.83%), respectively). Positive associations were also observed between PFNA, PFUnDA, perfluorooctane sulfonate (PFOS), and 6:2 Cl-PFESA and low-density lipoprotein cholesterol. However, no associations between PFASs and hemoglobin A1c, triglycerides, or high-density lipoprotein cholesterol reached statistical significance, nor associations between PFAS mixtures and outcomes of interest. In conclusion, the significant correlations between serum PFASs and glycemic biomarkers and lipid fractions indicated that PFAS exposure may be a potential diabetogenic factor. To the best of our knowledge, this is the first study to assess the associations between novel Cl-PFESAs and type 2 diabetes, although the inverse associations observed require clarification in future studies.

Introduction: Metabolic syndrome (MetS) is one contributing factor to cardiovascular diseases (CVD). Although there have been several reports showing MetS to be a risk factor for CVD, there are limited data available on which of the diagnostic criteria for MetS carries the greatest risk for CVD in the elderly population. This study thus aimed to evaluate these criteria in terms of risk of CVD in this population. Methods: This was a retrospective cohort study conducted at three referral hospitals in Thailand. The study period was between January 1, 2007 and December 31, 2016. Eligible patients were identified whether presence of MetS or not at the beginning of study and followed until the end of study. The primary outcome of study was presence of CVD. Predictors for CVD were analyzed by Cox proportional-hazards regression. Results: During the study period, there were 1080 patients who met the study criteria, 253 (23.42%) of whom had CVD. There were five factors significantly associated with CVD occurrence including age, smoking, SBP, FPG, and HDL-c. The two factors with the highest adjusted hazard ratio were FPG and SBP at 2.92 and 2.34, respectively. Conclusions: The three MetS criteria including SBP, FPG, and HDL-c may be predictors for cardiovascular diseases in elderly populations. Physician may need to focus on these particular factors of MetS in terms of CVD prevention in elderly patients.

Background: Metabolic syndrome (MetS) is a multifactorial disorder and a predisposing factor for diabetes, heart diseases, and stroke. Glycated haemoglobin (HbA1c) has recently received considerable attention as a potential marker to identify subjects at risk of MetS. This study aimed at assessing the performance of fasting plasma glucose (FPG), the American Diabetes Association (ADA) HbA1c cut-off, and a population-derived HbA1c (pHbA1c) cut-off value as the glycaemic criterion for MetS in a non-diabetic population. Methods: In this cross-sectional study, we recruited 728 non-diabetic Ghanaian adults. Venous blood sample was obtained and fasting plasma insulin and glucose, HbA1c, lipid profile, blood pressure and anthropometric measurements were performed for each respondent. Results: The prevalence of MetS using the FPG, ADA HbA1c and pHbA1c criteria were 35.2%, 38.5% and 41.8%, respectively. The pHbA1c cut-off identified 6.6% and 3.3% more subjects with MetS when compared with FPG and the ADA HbA1c cut-offs, respectively while the ADA HbA1c cut-off identified 3.3% more subjects with MetS compared with the FPG criterion. The ADA HbA1c criterion showed a substantial agreement (ĸ = 0.79) with the FPG criterion while pHbA1c showed an almost perfect concordance (ĸ = 0.82) with the FPG criterion and an excellent sensitivity and specificity for identifying subjects with MetS in the study population. Conclusion: Screening of MetS by introduction of the ADA HbA1c criterion in addition to the traditional FPG criterion enhances the detection of more people with MetS. However, the use of population-derived HbA1c cut-off value could potentially identify even greater number of high risk subjects in that specific population.

Background: There remains uncertainty regarding whether a single fasting glucose measurement is sufficient to predict risk of adverse perinatal outcomes. Methods: We included 12,594 pregnant women who underwent a 75-g oral glucose-tolerance test (OGTT) at 22–28 weeks' gestation in the Born in Guangzhou Cohort Study, China. Outcomes were large for gestational age (LGA) baby, cesarean section, and spontaneous preterm birth. We calculated the area under the receiver operator characteristic curves (AUCs) to assess the capacity of OGTT glucose values to predict adverse outcomes, and compared the AUCs of different components of OGTT. Results: 1325 women had a LGA baby (10.5%). Glucose measurements were linearly associated with LGA, with strongest associations for fasting glucose (odds ratio 1.37, 95% confidence interval 1.30–1.45). Weaker associations were observed for cesarean section and spontaneous preterm birth. Fasting glucose have a comparable discriminative power for prediction of LGA to the combination of fasting, 1 h, and 2 h glucose values during OGTT (AUCs, 0.611 vs. 0.614, P = 0.166). The LGA risk was consistently increased in women with abnormal fasting glucose (≥5.1 mmol/l), irrespective of 1 h or 2 h glucose levels. Conclusions: A single fasting glucose measurement performs comparably to 75-g OGTT in predicting risk of having a LGA baby.

Exposure to persistent organic pollutants may be associated to type 2 diabetes, but the studies on associations between short-chain chlorinated paraffin (SCCP) exposure and type 2 diabetes risk in humans are still scarce. Here, we conducted a case-control study involving 344 participants in Shandong Province, East China, to explore the effects of SCCPs on type 2 diabetes risk and their correlations with glycemic biomarker and serum lipid parameters. SCCPs were detected in all serum samples with a median concentration of 24 ng mL -1 in cases and 19 ng mL -1 in controls. Exposure to C 10 -CPs, C 11 -CPs, and ΣSCCPs were positively associated with the risk of type 2 diabetes after adjusting for confounders. The associations remained consistent in stratified analyses but stronger in male participants and obese individuals. In the control group, there were significant and positive correlations between SCCP exposure and levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), total lipid, and non-high-density lipoprotein-cholesterol. Significant joint effects on SCCP exposure and lipid parameters were observed in females when analyzed by the quantile-based g-computation model, and C 10 -CPs showed the highest contribution. Mediation analysis showed that LDL-C had significant mediation effects on the associations between C 10 -CPs, C 11 -CPs, and ΣSCCPs exposure and risk of type 2 diabetes. Moreover, TC and high-density lipoprotein-cholesterol were mediators in the relationship between C 11 -CPs and type 2 diabetes. Taken together, our study revealed that human exposure to SCCPs may increase the risk of type 2 diabetes and disrupt lipid metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: Bempedoic acid significantly lowers low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia but its effects in patients with metabolic syndrome (MetS) have not been well characterized. We sought to determine the efficacy and safety of bempedoic acid in patients with hypercholesterolemia by baseline MetS status., Methods: This study used pooled data from four phase 3 studies. Using modified International Atherosclerosis Society guidelines, patients were grouped into two pools: those with and those without MetS. Patients with diabetes were excluded. Endpoints assessed change from baseline to week 12 in lipid and glycemic parameters and high-sensitivity C-reactive protein (hsCRP), and safety., Results: The study included 936 patients with MetS (bempedoic acid, 648; placebo, 288) and 1573 without MetS (bempedoic acid, 1037; placebo, 536). Significant placebo-corrected reductions in LDL-C were observed with bempedoic acid (p < 0.0001), with a slightly larger decrease in patients with vs. without MetS (-22.3% vs. -18.4%; interaction p = 0.0472). Compared with placebo, bempedoic acid significantly (p < 0.0001) lowered total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and hsCRP, with a similar magnitude of benefit observed between MetS categories. Triglycerides increased with bempedoic acid but only to a lesser extent than with placebo in patients without MetS (placebo-corrected difference, -4.4%; p = 0.02). Only patients with MetS experienced decreases in glycated hemoglobin (-0.07%; p < 0.0001) and fasting plasma glucose (-2.4 mg/dL; p = 0.002). Safety was comparable between MetS categories and treatment groups., Conclusions: These data suggest that bempedoic acid is a suitable therapy for patients with and without MetS who require additional lipid lowering., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MDS has received research grant(s)/support paid to his institution from Amgen, Esperion Therapeutics, Ionis Pharmaceuticals, the National Institutes of Health, NewAmsterdam Pharma, and Novartis, and honoraria for consultancy from EmendoBio, Ionis Pharmaceuticals, Novartis, and Regeneron Pharmaceuticals. He has also served on scientific advisory boards for Amgen, Novartis, and Precision BioSciences. PRT has received funding/grant support from the American Heart Association, the National Institutes of Health, and the Federal Emergency Management Agency, and honoraria for consultancy from Amgen, Bayer, Boehringer Ingelheim, Esperion Therapeutics, Medtronic, Novartis, Novo Nordisk, and Sanofi. MJL is an employee of Esperion Therapeutics, Inc. LL is a consultant for Esperion Therapeutics, Inc. CMB has received research grant(s)/support paid to his institution from Abbott Diagnostics, Akcea Therapeutics, Amarin, Amgen, Esperion Therapeutics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, Roche Diagnostics, Sanofi Synthelabo, the National Institutes of Health, the American Heart Association, and the American Diabetes Association; he has also served as a consultant for Abbott Diagnostics, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Intercept Pharmaceuticals, Ionis Pharmaceuticals, Matinas BioPharma Holdings, Merck, Novartis, Novo Nordisk, Regeneron Pharmaceuticals, Roche Diagnostics, and Sanofi Synthelabo., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The associations and potential mechanisms of low to moderate arsenic exposure with fasting plasma glucose (FPG) and type 2 diabetes mellitus (T2DM) are still unclear. To assess the effects of short-term and long-term arsenic exposure on hyperglycemia and the mediating effect of oxidative damage on such association, three repeated-measures studies with 9938 observations were conducted in the Wuhan-Zhuhai cohort. The levels of urinary total arsenic, FPG, urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2α), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and plasma protein carbonyls (PCO) were measured. Generalized linear mixed models were used to evaluate the exposure-response relationships of urinary total arsenic with FPG and the prevalent risks of impaired fasting glucose (IFG), T2DM, and abnormal glucose regulation (AGR). Cox regression models were applied to assess the associations of arsenic exposure with incident risks of IFG, T2DM, and AGR. Mediation analyses were performed to assess the mediating effects of 8-iso-PGF2α, 8-OHdG, and PCO. In cross-sectional analyses, each one-unit increase in natural log-transformed urinary total arsenic was associated with a 0.082 (95% CI: 0.047 to 0.118) mmol/L increase in FPG, as well as a 10.3% (95% CI: 1.4%-20.0%), 4.4% (95% CI: 5.3%-15.2%), and 8.7% (95% CI: 1.2%-16.6%) increase in prevalent risks of IFG, T2DM, and AGR, respectively. In longitudinal analyses, arsenic exposure was further associated with the annual increased rate of FPG with a β (95% CI) of 0.021 (95% CI: 0.010 to 0.033). The incident risks of IFG, T2DM, and AGR were increased without statistical significance when arsenic levels increased. Mediation analyses showed that 8-iso-PGF2α and PCO mediated 30.04% and 10.02% of the urinary total arsenic-associated FPG elevation, respectively. Our study indicated that arsenic exposure was associated with elevated level and progression rate of FPG among general Chinese adults, where lipid peroxidation and oxidative protein damage might be the potential mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Styrene and ethylbenzene (S/EB) are hazardous pollutants that have attracted worldwide concern. In this prospective cohort study, S/EB exposure biomarker (the sum of mandelic acid and phenylglyoxylic acid [MA+PGA]) and fasting plasma glucose (FPG) were repeatedly measured three times. The polygenic risk score (PRS) based on 137 single nucleotide polymorphisms for type 2 diabetes mellitus (T2DM) was calculated to evaluate cumulative genetic effect. In repeated-measures cross-sectional analyses, MA+PGA (β [95% confidence interval]: 0.106 [0.022, 0.189]) and PRS (0.111 [0.047, 0.176]) were significantly related to FPG. For long-term effect assessment, participants with sustained high MA+PGA or with high PRS had 0.021 (95% CI: -0.398, 0.441) or 0.465 (0.064, 0.866) mmol/L increase in FPG, respectively, over 3 years follow-up, and had 0.256 (0.017, 0.494) or 0.265 (0.004, 0.527) mmol/L increase in FPG, respectively, over 6 years follow-up. We further detected a significant interaction effect between MA+PGA and PRS on FPG change, compared with participants with sustained low MA+PGA and low PRS, those with sustained high MA+PGA and high PRS had 0.778 (0.319, 1.258) mmol/L increase in FPG (P for interaction=0.028) over 6 years follow-up. Our study provides the first evidence that long-term exposure to S/EB potentially increases FPG, which might be aggravated by genetic susceptibility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The risk of hepatocellular carcinoma (HCC) is associated with a variety of factors. However, the possible association between the abnormal metabolism of fasting plasma glucose (FPG) and alanine aminotransferase (ALT) and the risk of HCC has not been widely studied. We examined this relationship based on a prospective cohort study., Methods: 162 first-attack HCC cases during three follow-up periods (2014-2020) were selected as the case group. A control group of 648 participants was obtained by 1:4 matching of age (± 2 years) and sex with noncancer participants in the same period. Conditional logistic regression models, restricted cubic spline models, additive interaction models, and generalized additive models were used to explore the effects of FPG and ALT on the risk of HCC., Results: After correction for confounding factors, we found that abnormal FPG and elevated ALT increased the risk of HCC, respectively. Compared with the normal FPG group, the risk of HCC was significantly increased in the impaired fasting glucose (IFG) (OR = 1.91, 95 %CI: 1.04, 3.50) and diabetes groups (OR = 2.12, 95 %CI: 1.24, 3.63). Compared with the lowest quartile of ALT, subjects in the fourth quartile had an 84 % increased risk of HCC (OR = 1.84, 95 %CI: 1.05-3.21). Moreover, there was an interaction between FPG and ALT on the risk of HCC, and 74 % of the HCC risk could be attributed to their synergistic effect (AP = 0.74, 95 %CI: 0.56-0.92)., Conclusion: Abnormal FPG and elevated ALT are independent risk factors for HCC, and they have a synergistic effect on the risk of HCC. Therefore, serum FPG and ALT levels should be monitored to prevent the development of HCC., Competing Interests: Declaration of Competing Interest All authors declare no interests of competing., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The alternative flame retardants, novel brominated flame retardants (NBFRs) and organophosphate flame retardants (OPFRs) are ubiquitous in the environment and biota and may induce endocrine disruption effects. Associations between traditional endocrine-disrupting chemicals and type 2 diabetes have been extensively reported in epidemiological studies. However, the effects of NBFRs and OPFRs in humans have not been reported to date. This paper reports a case-control study of 344 participants aged 25-80 years from Shandong Province, East China, where potential associations between serum NBFR and OPFR concentrations and type 2 diabetes are assessed for the first time. After adjusting for covariates (i.e., age, sex, body mass index, smoking status, alcohol consumption, triglycerides, and total cholesterol), serum concentrations of pentabromotoluene, 2,3-dibromopropyl 2,4,6-tribromophenyl ether, tri-n-propyl phosphate, triphenyl phosphate, and tris (2-ethylhexyl) phosphate were significantly positively associated with type 2 diabetes. In the control group, decabromodiphenyl ethane and triphenyl phosphate were significantly positively associated with fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol. In the quantile g-computation model, significant positive mixture effect was found between the flame retardants mixtures and high-density lipoprotein cholesterol levels, and decabromodiphenyl ethane contributed the largest positive weights to the mixture effect. Overall, these findings suggest that exposure to NBFRs and OPFRs may promote type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: This study aimed to identify unique dietary patterns, and to examine the correlation of dietary patterns with elevated blood pressure, lipid profile and fasting plasma glucose (FPG) among adults in Jiangsu Province of China., Methods and Results: 4951 individuals were selected in this cross-sectional study from nutrition and health survey in Jiangsu Province in 2014. Factor analysis was used to identify the dietary patterns. Higher quartile of the cereals-seafood-dairy dietary pattern was inversely associated with high low-density lipoprotein cholesterol (LDL) (composed to Q1, OR = 0.834, 95% CI: 0.700∼0.993, P < 0.05) and FPG (composed to Q1, OR = 0.725, 95% CI: 0.609-0.862, P < 0.05), while higher quartile of the traditional Jiangsu dietary pattern was positively associated with low high-density lipoprotein cholesterol (HDL) (composed to Q1, OR = 1.395, 95% CI: 1.067∼1.825, P < 0.05) and high systolic blood pressure (SBP) (composed to Q1, OR = 1.238, 95% CI: 1.020∼1.503, P < 0.05). Higher scores of the refined food-oriented dietary pattern was inversely related to high triglycerides (TG) (composed to Q1, OR = 0.665, 95% CI: 0.551∼0.802, P < 0.05), but was positively related to high TC (composed to Q1, OR = 2.179, 95% CI: 1.817∼2.614), high LDL (composed to Q1, OR = 2.431, 95% CI: 2.037∼2.902, P < 0.05) and elevated FPG (composed to Q1, OR = 1.734, 95% CI: 1.458∼2.061, P < 0.05)., Conclusion: Different structure of dietary patterns do affect the blood pressure, lipid profile and fasting plasma glucose among adults in Jiangsu Province, China., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Many metals are involved in the pathogenesis of diabetes, but most of existing studies focused on single metals. The study of mixtures represents real-life exposure scenarios and deserves attention. This study aimed to explore the potential relationship of urinary copper (Cu), zinc (Zn), arsenic (As), selenium (Se), and strontium (Sr) contents with fasting plasma glucose (FPG) levels in 2766 participants. The levels of metals in urine were determined by inductively coupled plasma-mass spectrometry. We used linear regression models and the Bayesian kernel machine regression (BKMR) to evaluate the association between metals and FPG levels. In the multiple metals linear regression, Zn (β = 0.434), Se (β = 0.172), and Sr (β = -0.143) showed significant association with FPG levels (all P < 0.05). The BKMR model analysis showed that the results of single metal association were consistent with the multiple metals linear regression. The mixture of five metals had a positive over-all effect on FPG levels, and Zn (PIP = 1.000) contributed the most to the FPG levels. Cu and As were negatively correlated with FPG levels in women. The potential interaction effect between Cu and Sr was observed in participants aged ≥ 60 years old (P interaction = 0.035). In summary, our results suggested that multiple metals in urine are associated with FPG levels. Further studies are needed to confirm these findings and clarify the underlying mechanisms., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy., Methods: A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75 g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n = 59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n = 94); combined group (FPG&1h/2h-PG group; n = 42). Non-GDM pregnancies were included (n = 485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis., Results: Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p < 0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR] = 2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR = 2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR = 2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR = 2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference)., Conclusions: Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM., Competing Interests: Conflicts of interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Gestational Diabetes Mellitus (GDM) is associated with a well-documented range of adverse pregnancy outcomes. The present meta-analysis was conducted to evaluate the effects of vitamin D supplementation on glycemic control and maternal-neonatal outcomes in women with established GDM., Methods: Published literature was retrieved and screened from PubMed, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang, and Cochrane Center Register of Controlled Trails up to May 2020. RCTs of vitamin D supplementation on pregnant women with GDM were included., Results: 19 RCTs (1550 participants) were eligible for meta-analyses. Overall, vitamin D supplementation significantly reduced serum fasting plasma glucose (FPG) (MD: -10.20 mg/dL, 95%CI: -13.43 to -6.96), insulin concentration (MD: -5.02 μIU/mL, 95%CI: -6.83 to -3.20) and the homeostasis model assessment of insulin resistance (HOMA-IR) (MD:-1.06, 95%CI: -1.40 to -0.72) in women with GDM. In addition, vitamin D supplementation in pregnant women with GDM significantly reduced adverse maternal outcomes including cesarean section (RR: 0.75, 95%CI: 0.63 to 0.89), maternal hospitalization (RR: 0.13, 95%CI: 0.02 to 0.98) and postpartum hemorrhage (RR: 0.47, 95%CI: 0.22 to 1.00). Several adverse neonatal complications including neonatal hyperbilirubinemia (RR: 0.47, 95%CI: 0.33 to 0.67), giant children (RR: 0.58, 95%CI: 0.38 to 0.89), polyhydramnios (RR: 0.42, 95% CI: 0.24 to 0.72), fetal distress (RR: 0.46, 95%CI: 0.24 to 0.90) and premature delivery (RR: 0.43, 95% CI: 0.26 to 0.72) were also significantly reduced., Conclusions: This meta-analysis suggested that supplementation of GDM women with vitamin D may lead to an improvement in glycemic control and reduction of adverse maternal-neonatal outcomes., Competing Interests: Conflict of interest None of the other authors reported a conflict of interest related to the study., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Studies with multi-pollutant approach on the relationships between multiple metals and fasting plasma glucose (FPG) are limited. Few studies are available on the potential sex-specific associations between metal exposures and glucose metabolism. We explored the associations between 22 plasma metals and FPG level among the 769 participants from the manganese-exposed workers healthy cohort in China. We applied a sparse partial least squares (sPLS) regression followed by ordinary least-squares regression to evaluate multi-pollutant association. Bayesian kernel machine regression (BKMR) model was used to deal with metal mixtures and evaluate their joint effects on FPG level. In the sPLS model, negative associations on FPG levels were observed for plasma iron (belta = -0.066), cobalt (belta = -0.075), barium (belta = -0.109), and positive associations for strontium (belta = 0.082), and selenium (belta = 0.057) in men, which overlapped with the results among the overall participants. Among women, plasma copper (belta = 0.112) and antimony (belta = 0.137) were positively associated with elevated FPG level. Plasma magnesium was negatively associated with FPG level in both sexes (belta = -0.071 in men and belta = -0.144 in women). The results of overlapped for plasma magnesium was selected as the significant contributor to decreasing FPG level in the multi-pollutant, single-metal, and multi-metal models. BKMR model showed a significantly negative over-all effect of six metal mixtures (magnesium, iron, cobalt, selenium, strontium and barium) on FPG level among the overall participants from all the metals fixed at 50th percentile. In summary, our findings underline the probable role of metals in glucose homeostasis with potential sex-dependent heterogeneities, and suggest more researches are needed to explore the sex-specific associations of metal exposures with risk of diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To screen 97 obese Arab adolescents for metabolic risk factors., Results: Insulin resistance, metabolic syndrome and intermediate hyperglycaemia was found in 56.7 %, 14.4 % and 27.8 % (HbA1c) while fasting plasma glucose was impaired in 0-16.5 %, using different cut-offs. Interventions to prevent obesity and diabetes are needed., (Copyright © 2020 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Exposure to 1-bromopropane (1-BP) has been reported to cause glutathione depletion and increase the level of oxidative damage, which play critical roles in diabetes. However, the possible associations or mechanisms of the exposure of 1-BP with the plasma glucose level and the risk of diabetes are unclear. In this study, we explored the relationships of the urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-l-cysteine (BPMA) with fasting plasma glucose (FPG) levels and the risk of diabetes, and the mediating role of oxidative damage in the above relationships in 3678 urban adults from the Wuhan-Zhuhai cohort in China. We found a significant dose-response relationship between BPMA and FPG levels with a β of 0.09 (95 % CI: 0.04, 0.14). In addition, mediating effect of urinary BPMA on FPG levels was observed depending on elevated 8-isoprostane level, with a median proportion of 32.06 %. Furthermore, we observed a significant association between urinary BPMA and the risk of diabetes, with an adjusted odds ratio of 1.34 (1.18, 1.52) for all participants. These results indicated that urinary 1-BP metabolites were positively associated with FPG levels and the risk of diabetes among urban adults in this cross-sectional study. Lipid peroxidation partially mediated the association between urinary 1-BP metabolites and FPG levels., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Previous studies investigating the association between PM 2.5 exposure and fasting plasma glucose levels (FPGLs) are mostly limited to short- and mid-term PM 2.5 exposure and lack adjustments for key confounders in adult research., Objectives: Exploring the relationship between seven years long-term PM 2.5 exposure and FPGLs in Chinese children and adolescents aged 6-17 years., Methods: Between September 2013 and December 2013, 16,489 participants aged 6-17 years were recruited using a four-staged, stratified, cluster sampling strategy from 7 provinces, autonomous regions and municipalities of mainland China. A generalized linear mixed model (GLMM) was used to estimate the relationship between annual PM 2.5 exposure (2007-2013) and FPGLs stratified by sex and one-year age increments. Sociodemographic characteristics, living with both parents, early-life factors, behaviours, and infection symptoms were gradually adjusted from the crude model to regression model 6, and BMI was adjusted for in model 7., Results: The annual concentration of PM 2.5 was 56.23 (±12.99) μg/m 3 . The mean FPGLs in the 8551 boys (4.75 mmol/L ± 0.52) was significantly higher than that in the 8194 girls (4.63 mmol/L ± 0.48) (P < 0.0001). In model 6, for every 10 μg/m3 increase in PM 2.5 exposure, the FPGLs in boys and girls increased by 0.048 (95% CIs 0.031 to 0.065) mmol/L (P < 0.0001) and 0.054 (95% CIs 0.039 to 0.069) mmol/L (P < 0.0001), respectively. The FPGLs were significantly positively associated with long-term PM 2.5 exposure at the ages of 12, 15 and 16 years in both the boys and girls and exhibited age differences in model 7. The prevalence of impaired fasting plasma glucose (IFP) and diabetes decreased by 0.8% when the exposure concentration of PM 2.5 was reduced by 10 μg/m 3 in model 6, which assessed the negative effects of PM 2.5 exposure and revealed that 1,298,920 children and adolescents could have been protected from IFP and diabetes in 2013 in China., Conclusions: Long-term PM 2.5 exposure may be an independent risk factor of elevated FPGLs. The adverse effect of PM 2.5 exposure on FPGLs in children and adolescents could appear after 10 years of cumulative exposure. The precise intervention time was revealed as approximately 12 and 11 years in boys and girls, respectively. There are great public health implications associated with early prevention strategies for the eradication of the negative effects of long-term exposure to PM 2.5 on FPGLs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier B.V.)

Background & Aims: As vitamin D deficiency is associated with an increased risk of gestational diabetes mellitus (GDM), we aimed to test vitamin D supplementation as a strategy to reduce GDM risk (evaluated after fasting plasma glucose (FPG), insulin resistance and weight gain) in pregnant overweight/obese women., Methods: The DALI vitamin D multicenter study enrolled women with prepregnancy body mass index (BMI) ≥ 29 kg/m 2 , ≤19 + 6 weeks of gestation and without GDM. Participants were randomized to receive 1600 IU/day vitamin D3 or placebo (each with or without lifestyle intervention) on top of (multi)vitamins supplements. Women were assessed for vitamin D status (sufficiency defined as serum 25-hydroxyvitamin D (25(OH)D) ≥ 50 nmol/l), FPG, insulin resistance and weight at baseline, 24-28 and 35-37 weeks. Linear or logistic regression analyses were performed to assess intervention effects., Results: Average baseline serum 25(OH)D was ≥50 nmol/l across all study sites. In the vitamin D intervention arm (n = 79), 97% of participants achieved target serum vitamin 25(OH)D (≥50 nmol/l) at 24-28 weeks and 98% at 35-37 weeks vs 74% and 78% respectively in the placebo arm (n = 75, p < 0.001). A small but significantly lower FPG (-0.14 mmol/l; CI95 -0.28, -0.00) was observed at 35-37 weeks with the vitamin D intervention without any additional difference in metabolic status, perinatal outcomes or adverse event rates., Conclusion: In the DALI vitamin D trial, supplementation with 1600 IU vitamin D3/day achieved vitamin D sufficiency in virtually all pregnant women and a small effect in FPG at 35-37 weeks. The potential of vitamin D supplementation for GDM prevention in vitamin D sufficient populations appears to be limited., Trial Registration Number: ISRCTN70595832., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Organochlorine pesticides (OCPs) have been reported to be associated with an elevated risk of type 2 diabetes, although no study has focused on such associations in Chinese populations. In this case-control study, we aimed to explore the associations between OCPs and type 2 diabetes and their potential mechanisms in a population from East China. Participants diagnosed with type 2 diabetes and nondiabetic participants from Shandong Province, East China, were enrolled in this case-control study. Six OCPs (β-HCH, trans-chlordane, trans-nonachlor, p,p'-DDE, p,p'-DDT and mirex/kepone) were detected in more than 75% of serum samples. Logistic regression analysis and multiple linear regression analysis were used to assess the associations between OCP exposure and the outcomes. After adjusting for potential confounding factors such as age, sex and body mass index, all six OCPs showed positive associations with type 2 diabetes in a linear dose-response manner. Serum concentrations of β-HCH and p,p'-DDE were associated with higher levels of fasting plasma glucose in participants without diabetes, although no OCPs showed significant associations with hemoglobin A1c. In addition, certain OCPs showed significantly positive associations with triglycerides, total cholesterol, and low-density lipoprotein cholesterol and negative relationships with high-density lipoprotein cholesterol in nondiabetics, indicating that OCP exposure may disrupt lipid metabolism. Findings in the current study indicated that OCPs may be a diabetogenic factor in the population of this study. To our knowledge, this is the first study to investigate the associations between OCP exposure and type 2 diabetes in a Chinese population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The goal of this study was to detect novel modified forms of hemoglobin using mass spectrometry (MS) and to investigate the effect of modified hemoglobin on HbA1c and fasting plasma glucose (FPG)., Methods: This study was conducted on 1200 subjects aged >25 years. Hemoglobin from the above-mentioned subjects was detected using direct-infusion electrospray ionization-MS, and HbA1c and FPG were measured according to the manufacturer's instructions. Regression analysis was performed to estimate the correlations and interactions among HbA1c, FPG, and modified hemoglobin., Results: Multiple modified forms (α 1 , α 2 , α 3 , β 1 , β 2 , and β 3 ) of hemoglobin were observed using MS. Statistical analyses indicated that modified hemoglobin was significantly correlated with FPG (p ≤ .01). The association of FPG with α 1 % (p = .021) and β 3 % (p < .001) values was independent of HbA1c% and other modified forms of hemoglobin. Interaction analyses implied two significant interaction effects of HbA1c% with gender (β = -0.184, p = .007) and α 3 % (β = -0.104, p < .001) on FPG. The relationship between HbA1c% and FPG was stronger in males than in females, and a decreased level of α 3 % also affected the association of HbA1c% and FPG., Conclusions: This MS-based method is an effective tool for monitoring glycated forms of hemoglobin than traditional approaches. For the Han Chinese population, multiple-glycated hemoglobin affects the association of FPG with HbA1c%, and the correlation between FPG and HbA1c% in females is different from that in males. These data suggest that the HbA1c criteria for the diagnosis and monitoring of diabetes should be established according to genders and modified types of hemoglobin., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cardiovascular disease is a one of most common causes of mortality around the world. This meta-analysis aims to summarize and conclude the clinical evidence regarding the use of saffron and its constituents, in particular crocin, on cardiovascular risk factors. A systematic review was conducted with PubMed, Scopus, Web of Science, Cochrane library and Google Scholar up to 24 May 2018. Randomized controlled trials (RCTs) that assessed the clinical effects of saffron and/or its constituents on blood lipid profile, glycemic parameters, blood pressure and anthropometric indices in human subjects were included. Eleven publication from ten studies comprising 622 participants included in quantitative analysis. Pooling of results showed significant effect of saffron on diastolic blood pressure (-1.24 mmHg; 95% CI: -1.51 to -0.96; I 2  = 0%), body weight (-1.29 kg; 95% CI: -2.14 to -0.44; I 2  = 70%) and waist circumstance (-1.68 cm; 95% CI: -3.31 to -0.04; I 2  = 51%). When subgroup analysis was performed based on quality of studies, a significant reduction in fasting plasma glucose levels was observed in subgroup with high quality studies (-10.14 mg/dl; 95% CI: -13.80 to -6.48; I 2  = 0%). Meta-analysis did not reveal any significant change in lipid profile, fasting insulin, systolic blood pressure and body mass index following saffron consumption. Present meta-analysis suggests that saffron might be beneficial in several outcomes related with cardiovascular disease. However, further RCTs with long term intervention with different dose of administration are needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In subjects who present a first fasting plasma glucose (FPG 1 ) ≥7.0mmol/l without classic symptoms of diabetes, diagnosis of diabetes will likely be missed without an additional oral glucose tolerance test (OGTT) in the Chinese population. Recent studies have shown that glycated albumin (GA) has advantages in reflecting postprandial hyperglycemia. Therefore, the present study evaluated whether additional measurement of GA could reduce the rate of missed diagnosis of diabetes., Methods: A total of 1287 participants (711 men, 576 women) with a FPG 1 ≥7.0mmol/l without classic symptoms of diabetes were enrolled and underwent a 75-g OGTT. Serum GA was measured by a liquid enzyme method. Diabetes was diagnosed based on the 2010 American Diabetes Association (ADA) criteria., Results: A total of 992 (77.08%) participants were diagnosed diabetes by OGTT and glycated hemoglobin A 1c (HbA 1c ). The diagnostic validity of 2-h postload plasma glucose (2hPG) was superior to other glycemic index (the diagnostic sensitivity of 2hPG, HbA 1c , the second FPG (FPG 2 ) was 87.50%, 73.99%, 63.21%, respectively). Without 2hPG after OGTT, repeat testing of FPG 2 alone would result in missed diagnosis of 36.79% of diabetic participants, whereas testing FPG 2 with HbA 1c was associated with a missed diagnosis rate of 14.31%. While using the combined criteria of FPG 2 ≥7.0mmol/l and/or HbA 1c ≥6.5% and/or GA≥17.1%, the rate of missed diagnosis was merely 9.48%. That is, the rate of missed diagnosis was reduced by 33.75% with the addition of GA measurement. The k value reflecting the consistency of diagnosis between the FPG 2 and/or HbA 1c and/or GA criteria and the 2010 ADA criteria was 0.788., Conclusions: For subjects with FPG 1 ≥7.0mmol/l without classic symptoms of diabetes, additional measurement of GA can help prevent missed diagnosis of diabetes in Chinese population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: This study assessed pre-diabetes (pre-DM) cutoffs for HbA1c and fasting plasma glucose (FPG) that were associated with an increased risk of incident DM., Methods: We evaluated 2267 non-diabetic Japanese health-check examinees (HbA1c: <6.5% [<48mmol/mol] and FPG: <7.0mmol/L) who were 30-79 years old and were followed-up for 5 years. Incident DM was defined as HbA1c of ≥6.5% (≥48mmol/mol), FPG of ≥7.0mmol/L, or physician-diagnosed DM., Results: During 11047 person-years, we identified 99 incident DM cases (4.3%). The incidence of DM increased with increasing baseline HbA1c or FPG levels, and the change points (95% confidence intervals) were 5.7% (5.6-5.7%; 39mmol/mol [38-39mmol/mol]) for HbA1c and 5.5mmol/L (5.5-5.6mmol/L) for FPG. The adjusted hazard ratios (HRs) for incident DM per one standard deviation-increase in HbA1c and FPG were 5.5 (4.4-6.8) and 4.0 (3.2-4.8), respectively. The adjusted HRs for incident DM were significantly higher at HbA1c of 5.7-6.4% (39-46mmol/mol) or FPG of 5.5-6.9mmol/L, compared to HbA1c of <5.7% (<39mmol/mol) or FPG of <5.5mmol/L., Conclusion: The lower cut-offs for pre-DM may be 5.7% (39mmol/mol) for HbA1c and 5.5mmol/L for FPG in this Japanese population., (Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Cinnamon (Cinnamomum sp) has been suggested to help patients with type 2 diabetes mellitus (T2DM) achieve better glycemic control, although conclusions from meta-analyses are mixed. To evaluate whether the use of cinnamon dietary supplements by adults with T2DM had clinically meaningful effects on glycemic control, as measured by changes in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c), a comprehensive PubMed literature search was performed. Eleven randomized controlled trials were identified that met our inclusion criteria that enrolled 694 adults with T2DM receiving hypoglycemic medications or not. In 10 of the studies, participants continued to take their hypoglycemic medications during the cinnamon intervention period. Studies ranged from 4 to 16 weeks in duration; seven studies were double-blind. Cinnamon doses ranged from 120 to 6,000 mg/day. The species of cinnamon used varied: seven used Cinnamomum cassia or Cinnamomum aromaticum, one used Cinnamomum zeylanicum, and three did not disclose the species. Because of the heterogeneity of the studies, a meta-analysis was not conducted. All 11 of the studies reported some reductions in FPG during the cinnamon intervention, and of the studies measuring HbA1c very modest decreases were also apparent with cinnamon, whereas changes in the placebo groups were minimal. However, only four studies achieved the American Diabetes Association treatment goals (FPG <7.2 mmol/L [130 mg/dL] and/or HbAlc <7.0). We conclude that cinnamon supplements added to standard hypoglycemic medications and other lifestyle therapies had modest effects on FPG and HbA1c. Until larger and more rigorous studies are available, registered dietitian nutritionists and other health care professionals should recommend that patients continue to follow existing recommendations of authoritative bodies for diet, lifestyle changes, and hypoglycemic drugs., (Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background and Aims: We aimed to determine if patient baseline characteristics affect responses to linagliptin and identify relevant predictors of glycated hemoglobin (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM)., Methods and Results: Data were pooled from three 24-week, placebo-controlled trials of similar design (linagliptin, n = 1651; placebo, n = 607). Patients were categorized according to baseline characteristics: age, T2DM duration, gender, body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and metabolic syndrome (MetS). Changes from baseline in HbA1c after 24 weeks were assessed with analysis of covariance (ANCOVA). The proportion of patients with baseline HbA1c >7% achieving HbA1c of ≤7% at week 24 were evaluated. Independent predictors of HbA1c response with linagliptin were analyzed in a multivariate analysis with ANCOVA. Linagliptin treatment led to significant mean (SE) placebo-corrected reductions from baseline in HbA1c across all subgroups (-0.42% [±0.11] to -0.79% [0.08]; all p < 0.001). Within subgroups, HbA1c reduction was more pronounced in patients without MetS (-0.74% [0.06]; treatment interaction p = 0.0489). The proportion of patients with baseline HbA1c >7% achieving a target HbA1c ≤7% was greater with linagliptin versus placebo (30.2% vs 11.5%; odds ratio 3.82; 95% CI 2.82 to 5.17; p < 0.001). Characteristics significantly predicting HbA1c reductions after 24 weeks were fasting plasma glucose and race (both p < 0.05)., Conclusion: This post-hoc analysis supports that linagliptin achieved clinically meaningful improvements in hyperglycemia in patients with diverse clinical characteristics. These improvements were more pronounced in patients without MetS., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: The present study aimed to evaluate the pregestational body mass index (preBMI) and initial fasting plasma glucose (FPG) in predicting gestational diabetes mellitus (GDM) in southern Chinese women., Study Design: A total of 327 pregnant women were recruited from the third affiliated hospital of Sun Yat-Sen University, Guangzhou, China. The preBMI and initial FPG at 16-18 weeks' gestation were measured. Oral glucose tolerance test was performed at 24-28 weeks' gestation. The sensitivity and specificity of preBMI and initial FPG as predictors for GDM were evaluated by receiver-operator characteristic curve analysis., Results: Both preBMI and initial FPG correlated with the 0-hour, 1-hour and 2-hour plasma glucose during oral glucose tolerance test (P < 0.05). The area under receiver-operator characteristic curve was 0.63 (95% CI: 0.57-0.68) for preBMI and 0.68 (95% CI: 0.61-0.72) for initial FPG in diagnosing GDM. The optimal cutoff for preBMI was 21.5 kg/m(2) (sensitivity 52.1% and specificity 69.2%) and 4.6 mmol/L (sensitivity 64.6% and specificity 65.2%) for initial FPG. Interestingly, the initial FPG had a better sensitivity compared to preBMI when the specificity was the same. Multivariate logistic regression analysis showed that initial FPG but not preBMI was the independent risk factor for the later development of GDM. After adjustment for the preBMI and the maternal age, the odds ratios of initial FPG and parity were 3.57 (95% CI: 1.72-7.45) and 2.11 (95% CI: 1.20-3.72)., Conclusions: Although both preBMI and initial FPG could be used as indicators for GDM, the initial FPG may be more suitable for predicting GDM in southern Chinese women., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications., Objective: We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status., Design: FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offspring's ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors., Results: At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (β = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (β = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo., Conclusion: Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI., (© 2016 American Society for Nutrition.)

Background and Aims: Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar)., Methods and Results: Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy., Conclusion: This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To assess the extent to which initial, intentional weight loss-associated improvements in glucose tolerance and insulin action are diminished with weight regain., Methods: 138 overweight and obese (BMI: 32.4±3.9kg/m(2)), adults (59.0±9.7 years), with pre-diabetes were followed through a 6-month weight loss intervention and subsequent 18-month weight maintenance period, or usual care control condition. Longitudinal change in weight (baseline, 6, 24 months) was used to classify individuals into weight pattern categories (Loser/Maintainer (LM), n= 50; Loser/Regainer (LR), n=51; and Weight Stable (WS), n=37). Fasting plasma glucose (FPG), insulin, and insulin resistance (HOMA-IR) were measured at baseline, 6, 12, 18 and 24 months and model adjusted changes, by weight pattern category, were assessed., Results: LMs and LRs lost 8.3±4.7kg (8.7±4.5%) and 9.6±4.7kg (10.2±4.7%) during the first 6 months, respectively. LM continued to lose 1.1±3.4kg over the next 18 months (9.9±6.5% reduction from baseline; p<0.05), while LRs regained 6.5±3.7kg (3.3±5.3% reduction from baseline; p<0.05). Weight change was directly associated with change in all DM risk factors (all p<0.01). Notably, despite an absolute reduction in body weight (from baseline to 24 months) achieved in the LR group, 24-month changes in FPG, insulin, and HOMA-IR did not differ between WS and LR groups. Conversely, LM saw sustained improvements in all measured DM risk factors., Conclusions: Significant weight loss followed by weight loss maintenance is associated with sustained improvements in FPG, insulin, and HOMA-IR; conversely, even partial weight regain is associated with regression of initial improvements in these risk factors towards baseline values., (Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Aims: To examine whether increasing fasting plasma glucose (FPG) levels were associated with worsening left ventricular (LV) diastolic function, independently of LV mass index (LVMI) in elderly, otherwise healthy subjects., Methods and Results: We tested cross-sectional associations between echocardiographically determined averaged E/é ratio/diastolic function, LVMI, cardiovascular risk factors, and FPG categorized as normal (NFG), impaired (IFG), and new-onset diabetes mellitus (DM), in 483 men and 208 women aged 56-79 years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >50%. Median E/é was significantly higher among subjects with diabetes than those without (8 vs. 7; p = 0.03), as was the prevalence of grade 2 or 3 diastolic dysfunction (25% vs. 16%; p = 0.02). E/é and diastolic function were significantly associated with LVMI (p ≤ 0.002), but not FPG category, on multivariable analysis. However, interaction analyses revealed that increasing LVMI was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG > 6 mmol/L (β=0.005 for IFG and DM vs. 0.001 for NFG; p = 0.02), whereas increasing systolic blood pressure was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG ≤ 6.9 mmol/L (β = 0.005 for NFG and 0.003 for IFG vs. -0.001 for DM; p=0.001)., Conclusion: Diastolic dysfunction was significantly more prevalent among patients with DM than those without. The importance of LVMI increased, but the importance of systolic blood pressure decreased with higher FPG category., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Prior studies have provided evidence that lifestyle change prevents or delays the occurrence of type 2 diabetes mellitus. The challenge is to translate research evidence for type 2 diabetes mellitus prevention into health care settings., Objective: We investigated the effect of medical nutrition therapy (MNT) compared with usual care on fasting plasma glucose values, glycated hemoglobin (HbA1c), serum lipid levels, and Diabetes Risk Score, from baseline to the end of a 12-week intervention in overweight or obese adults with prediabetes., Design: Prospective, randomized, parallel group study of 76 adults with impaired fasting plasma glucose or an HbA1c of 5.7% to 6.4%, recruited between April 2010 and May 2011 who completed a 12-week intervention period., Main Outcome Measures: The primary outcome measure was fasting plasma glucose. Secondary outcome measures were HbA1c, serum lipid levels, and Diabetes Risk Score., Statistical Analyses: A factorial repeated measures analysis of variance was used to make comparisons between the two groups (the MNT and usual care groups) and two measures of time (baseline and 12 weeks postintervention). Data analysis was performed using the Statistical Package for the Social Sciences (release 19.0, 2010, SPSS Inc)., Results: There was a significant interaction for group assignment and HbA1c (P=0.01), with the MNT group experiencing significantly lower HbA1c levels than the usual care group (5.79% vs 6.01%) after the 12-week intervention. There was a significant interaction for group assignment and Diabetes Risk Score (P=0.001). Diabetes Risk Score for the MNT group decreased from 17.54±3.69 to 15.31±3.79 compared with the usual care group score, which went from 17.23±4.69 to 16.83±4.73. Regardless of group assignment, both groups experienced a reduction in total cholesterol (P=0.01) and low-density lipoprotein cholesterol (P=0.04) level., Conclusions: The results demonstrate that individualized MNT is effective in decreasing HbA1c level in patients diagnosed with prediabetes., (Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Nutritional deficiencies are common after bariatric surgery, but few studies have examined them preoperatively. The objective of this study was to evaluate several vitamins, nutrients, and nutritional markers and their determinants in patients with obesity considering bariatric surgery., Methods: Preoperative values of fasting plasma glucose, insulin, lipid profile, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, thyroid-stimulating hormone, calcium, phosphate, albumin, magnesium, total proteins, liver function tests, iron, ferritin, folate, vitamin A, vitamin B12, selenium, and zinc were evaluated in 267 Caucasian outpatients (74.2% women, aged 40.5±12.6 years) who were considering bariatric surgery. The determinants of nutrient variability were analyzed by linear regression for nutrients with a prevalence of deficiency>10%, i.e., serum 25(OH)D, iron, phosphate, magnesium, and vitamin A., Results: Prevalence of inadequate concentrations was high for 25(OH)D (67.9% with values ≤ 20 ng/mL), magnesium (35.4%), phosphate (21.6%), iron (18.8%), and vitamin A (16.9%). Multiple deficiencies were common; 28.5%, 12.1%, and 6.3% of patients had 2, 3, and 4 deficiencies, respectively. In multivariate analyses, metabolic characteristics had an important impact on deficiencies, with lower values of 25(OH)D and vitamin A with increasing body mass index, lower values of 25(OH)D and magnesium with increasing fasting plasma glucose, and a positive correlation between vitamin A and triglycerides. Elevated TSH was associated with low iron concentrations., Conclusion: At all ages, micronutrient deficiencies were common, with high prevalence of concentration inadequacies for 25(OH)D, magnesium, phosphate, iron, and vitamin A. High body mass index and high fasting plasma glucose increased the risk of deficiencies, particularly for 25(OH)D. Preoperative screening and correction of deficiencies should be advised., (© 2014 American Society for Bariatric Surgery Published by American Society for Metabolic and Bariatric Surgery All rights reserved.)

Purpose: Although mean concentrations of hemoglobin A1c (A1C), fasting plasma glucose, and 2-hour plasma glucose differ by demographics, it is unclear what other characteristics of the distributions may differ, such as the amount of asymmetry of the distribution (skewness) and shift left or right compared with another distribution (shift)., Methods: Using kernel density estimation, we created smoothed plots of the distributions of fasting plasma glucose (N = 7250), 2-hour plasma glucose (N = 5851), and A1C (N = 16,209) by age, race-ethnicity, and sex in the 2005-2010 National Health and Nutrition Examination Survey, a nationally representative sample of U.S. adults including people with and without diabetes. We tested differences in distributions using cumulative logistic regression., Results: The distributions were generally unimodal and right-skewed. All distributions were shifted higher and more right-skewed for older age groups (P < .001 for each marker). Compared with non-Hispanic whites, the distribution of fasting plasma glucose was shifted higher for Mexican-Americans (P = .01), whereas the distribution of A1C was shifted higher for non-Hispanic blacks (P < .001). The distribution of fasting plasma glucose was shifted higher for men (P < .001) and the distribution of 2-hour plasma glucose was shifted higher for women (P = .01)., Conclusions: We provide a graphic reference for comparing these distributions and diabetes cut-points by demographic factors., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: This epidemiological study was done to generate normal ranges for the cholesterol and triglyceride levels in serum lipoprotein subclasses isolated from healthy adults based on gender and menopausal status., Methods: Cholesterol and triglyceride levels in 20 lipoprotein subclasses as separated by high performance liquid chromatography were measured in serum obtained from 825 fasting healthy subjects (267 men, 558 women)., Results: For serum cholesterol, 13.7% was found in very low density lipoprotein (VLDL) subclasses, 55.6% in low density lipoprotein (LDL) subclasses, and 30.4% in high density lipoprotein (HDL) subclasses. For serum triglycerides, these values were 52.1%, 27.9%, and 17.4%, respectively. Levels of cholesterol in some VLDL subclasses were inversely correlated with the levels of some HDL subclasses, while for triglycerides, elevated levels in any one subclass were generally strongly associated with elevated levels in all other subclasses. Men had significantly higher large VLDL-cholesterol levels than women (P < 0.05), while women had significantly higher small VLDL-cholesterol levels than men (P < 0.001). Women had significantly higher large LDL- and large and medium HDL-cholesterol levels than men (P < 0.001). Men had significantly higher chylomicron (CM), large and medium VLDL-, and small LDL-triglyceride levels than women (P < 0.001). Women had significantly higher very large and large HDL-triglyceride levels than men (P < 0.01). Postmenopausal women had significantly higher CM, all VLDL, and large, medium and small LDL-cholesterol levels, and significantly higher all VLDL, LDL, and HDL-triglyceride levels than premenopausal women (P < 0.001)., Conclusions: Our data document important gender and menopausal status differences in cholesterol and triglyceride subclass levels, as well as significant correlations between values in the various serum lipoprotein subclasses., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

A soluble form of CD26/dipeptidyl peptidase 4 (sCD26/DPP4) is found in serum and it has DPP4 enzymatic activity. We investigated whether the serum level of sCD26/DPP4 was influenced by the oral glucose tolerance test (OGTT) in healthy subjects. The serum sCD26/DPP4 level increased significantly from 824.5 ng/mL (interquartile range, from 699.0 to 1050 ng/mL) at baseline to a peak of 985.0 ng/mL (interquartile range, from 796.5 to 1215 ng/mL) during the OGTT (P < 0.0001). The peak sCD26/DPP4 level correlated positively with the baseline age and body mass index, and fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), alanine aminotransferase, and γ-glutamyl transpeptidase (GGT) levels whereas it correlated negatively with high-density lipoprotein (HDL) cholesterol and the serum levels of total and high-molecular weight (HMW) adiponectin. Stepwise regression analysis was done with forward selection of variables, including age, FPG, HOMA-IR, TG, HDL cholesterol, uric acid, GGT, C-reactive protein, and HMW adiponectin. In a model that explained 57.5% of the variation of the peak sCD26/DPP4 level, GGT (β = 0.382, P = 0.007) and HOMA-IR (β = 0.307, P = 0.034) were independent determinants of the peak serum level of sCD26/DPP4. Serum HMW adiponectin decreased significantly from 4.43 μg/mL (interquartile range, from 2.80 to 6.65 μg/mL) at baseline to 4.17 μg/mL (interquartile range, from 2.48 to 6.96 μg/mL) 120 minutes after the oral glucose load (P < 0.0001). The baseline serum level of sCD26/DPP4 showed a significant negative correlation with the percent change of HMW adiponectin during the OGTT. In conclusion, the serum level of sCD26/DPP4 increased acutely after an oral glucose load in apparently healthy subjects. The abrupt increase of serum sCD26/DPP4 after a glucose load may be a marker of insulin resistance that could come from liver or muscle., (Copyright © 2013 Mosby, Inc. All rights reserved.)