Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes.

BACKGROUND: Many previous studies have reported the association between iron overload (IO) and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanism is not clear. METHODS: Epidemiological data from the National Health and Nutrition Examination Survey 2017-2018 (NHANES) was used to systematically explore the association between IO and diabetes. Furthermore, transcriptome data from Gene Expression Omnibus (GEO) were analyzed using bioinformatics methods to explore the underlying functional mechanisms at the molecular level. RESULTS: Data from NHANES showed a "W" shape relationship between serum iron (frozen) and the risk of diabetes (P < 0.001) as well as a "∧" shape correlation between serum unsaturated iron binding capacity (UIBC) and the risk of diabetes (P = 0.007). Furthermore, the serum iron (frozen) was positively associated with fasting plasma glucose and HOMAB (P < 0.05), and UIBC was positively associated with fasting insulin (P < 0.05). Transcriptome data showed that two IO-related genes [Transferrin receptor (TFRC) and Solute carrier family-11 member-2 (SLC11A2)] were down-regulated in T2DM. The correlation analysis showed that expression levels of TFRC and SLC11A2 were significantly and positively correlated with genes involved in insulin secretion (P < 0.05). Protein-protein interaction network analysis showed that TFRC and SLC11A2 interacted with four key genes, including VAMP2, HIF1A, SLC2A1, and RAB11FIP2. CONCLUSION: We found that IO status was associated with increased FPG and aggravated HOMAB, and two IO-related genes (TFRC and SLC11A2) might induce the occurrence of T2DM by influencing insulin secretion, which provides potential therapeutic targets for T2DM patients.

Birth weight is associated with obesity and T2DM in adulthood among Chinese women.

BACKGROUND: Previous studies have indicated an association between birth weight (BW) and type 2 diabetes mellitus (T2DM), but few studies have explored this relationship under different conditions of obesity in adulthood. METHODS: A total of 4,005 individuals from ten provinces of China were randomly selected to participate in this study. We used a questionnaire to collect age, BW, current weight, height, T2DM history, age at T2DM diagnosis, and other variables. The participants were divided into three groups were according to BW trisection (BW ≤ 2500 g for the lower BW group, 2500 g < BW ≤ 3500 g for the normal BW group, and BW > 3500 g for the higher BW group). The cutoff of overweight and obesity were 25 kg/m2 and 28 kg/m2, respectively. RESULTS: The prevalence rates of T2DM among women with lower BW, normal BW and higher BW were 5.2%, 3.6% and 2.0%, respectively. The obesity prevalence rates in the lower BW, normal BW and higher BW groups were 8.1%, 6.7% and 9.0%, respectively. In the obese population, we did not find a relationship between BW and T2DM, but in the nonobese population, we found that with increasing BW, the risk of developing T2DM was reduced. Obese status in adulthood modified the association between BW and the risk of T2DM. CONCLUSION: There is a "U" shape association between BW and risk of adulthood obesity in Chinese women, but this trend is not existed between BW and risk of developing T2DM. In non-overweight females, the risk of developing T2DM decreased with increasing BW, but this trend was not observed in overweight females.

Lifestyle in adulthood can modify the causal relationship between BMI and islet function: using Mendelian randomization analysis.

BACKGROUND: Body mass index was intimately associated with islet function, which was affected by various confounding factors. Among all methods of statistical analysis, Mendelian randomization best ruled out bias to find the causal relationship. In the present study, we explored the relationship between 13 East Asian body mass index-related genes reported previously and islet function using the Mendelian randomization method. METHODS: A total of 2892 participants residing in northern China were enrolled. Anthropological information, such as sex, age, drinking status, smoking status, weight, height and blood pressure, was recorded for all participants. Fasting glucose and insulin were detected, and the insulin sensitivity index was calculated. 13 single nucleotide polymorphismss in East Asian body mass index -related genes were analysed with the ABI7900HT system. RESULTS: Five genetic locus mutations, CDKAL1, MAP2K5, BDNF, FTO and SEC16B, were found to be associated with body mass index and were used to estimate the genetic risk score. We found that the genetic risk score was negatively associated with the insulin sensitivity index. Even after adjusted of confounding factors, the relationship showed statistical significance. A subsequent interaction effect analysis suggested that the negative relationship between the genetic risk score and insulin sensitivity index no longer existed in the nondrinking population, and smokers had a stronger negative relationship than nonsmokers. CONCLUSION: We found a negative causal relationship between body mass index-related genetic locus mutations and insulin resistance, which might be increased by acquired lifestyle factors, such as drinking and smoking status.

Association of the CDKAL1 polymorphism rs10946398 with type 2 diabetes mellitus in adults: A meta-analysis.

Previous studies had reported that the CDKAL1 (cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1) rs10946398 C/A polymorphism associated with type 2 diabetes mellitus (T2DM) in various ethnic groups, however, inconsistent results have been obtained in studies of different populations.We performed a meta-analysis of 13 studies for rs10946398 of CDKAL1 on genetic susceptibility for T2DM.The results showed that CDKAL1 rs10946398 C/A polymorphism associated with T2DM under allelic (odds risk (OR): 1.17, 95% CI: 1.07-1.28, P = .0007), homozygous (OR: 1.39, 95% CI: 1.15-1.69, P = .0008), and dominant models (OR: 1.26, 95% CI: 1.09-1.46, P = .001).We found that rs10946398 C/A polymorphism was associated with T2DM, and this association was significantly in population of western country (Europe and United States) and Asian populations.

Metal Probe Microextraction Coupled to Dielectric Barrier Discharge Ionization-Mass Spectrometry for Detecting Drug Residues in Organisms.

In this study, a novel method for the direct coupling of metal probe microextraction (MPME) and a dielectric barrier discharge ionization (DBDI) source with mass spectrometry (MS) is reported. Analytes adsorbed on a tungsten needle were directly transferred to the DBDI source via rapid thermal desorption, which resulted in a limit of detection as low as 8 pg/mL. This is in part due to the "active capillary" configuration of the plasma ion source, where the efficiency of ion transfer to the MS is ∼100%. Specialty gases to maintain the plasma and carry analytes to the MS are not required. In contrast to direct one-step ionization of molecular adsorbates, the complete separation of the analyte desorption from the probe and the ionization event in our experimental setup greatly enhanced the sensitivity and detection reproducibility (RSD of 8.3%). We show detection of pyrimethamine, a first-line drug for the treatment and prevention of Plasmodium falciparum malaria all over the world, by this MPME/DBDI/MS method. The detection of drug residues in live fish and paramecium was achieved without the need for any sample pretreatment. The relative concentration of the drug in different organs of the fish was determined. This simple and convenient method has the potential for the analysis of chemicals even in single-cell organisms.

Six-year follow-up study on the association between white blood cell count and fasting blood glucose level in Chinese adults: A community-based health examination survey.

BACKGROUND: Pre-diabetes is considered to be an important reversible stage of type 2 diabetes (T2DM); thus, early identification of pre-diabetes may help in the prevention of T2DM. This study aimed to explore the relationship between white blood cell (WBC) counts and the cumulative risk of impaired fasting glucose (IFG) regulation at 6 years. METHODS: A community-based health examination survey was conducted among individuals who were randomly selected from 1300 residents living in China in 2010 to 2016. The participants were divided into four groups according to WBC baseline level. This study initially conducted a cross-sectional analysis of the population who underwent physical examination to explore the relationship between WBC count and FBG levels. Then, a follow-up study was conducted on the population who underwent IFG normal physical examination to explore the relationship between baseline WBC count and changes in FBG levels and the cumulative risk of 6-year IFG. RESULTS: During the 6-year cohort follow-up, 17.2% of the participants developed IFG, and the cumulative incidence rates of IFG in the four groups were 14.7%, 16.3%, 15.8%, and 22.2%. By Cox multiple regression equation the hazard ratio (HR) of the IFG increased by 18.7% for each additional unit of baseline WBC count with no adjustment of any factor. After adjusting factors, HR increased by 8.4%. CONCLUSION: Increased WBC counts are associated with risk of IFG, suggesting chronic inflammation may be involved in the development and progression of IFG.

Wingless-type MMTV integration site family member 5a: a novel biomarker regulated in type 2 diabetes mellitus and diabetic kidney disease.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is sustained by insulin resistance (IR) and reduced ß-cell mass, which is largely due to insulin secretory dysfunction. Wnt5a protein is essential to islet formation and ß-cell migration in the development of pancreas in vertebrates. Levels of the Wnt5a protein antagonist plasma secreted frizzled-related protein 5 (Sfrp5) were elevated in patients with T2DM. However, the association between Wnt5a, T2DM patients and diabetic kidney disease (DKD) is unknown. We aim to investigate the circulating Wnt5a levels in in different clinical stages of T2DM and evaluate its correlation of duration of diabetes mellitus chronic complication. METHODS: A total of 329 participants (187 males, 142 females; age range 40 to 80 years) were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters evaluated in subjects with new onset T2DM, onset T2DM after treatment and DKD at different clinical phases. RESULTS: Wnt5a was significantly down-regulated in newly diagnosed T2DM patients and gradually increased after 3 months of treatment. Interesting, serum wnt5a was gradually increased in patients with long-term diabetes and kidney disease compared to patients with T2DM and onset DKD. CONCLUSIONS: We speculated that the Wnt5a protein might regulate islet function and be involved in the onset of diabetes as a protective factor. It may be one of the inflammatory factors adversely involved in the progression of diabetic nephropathy.

Genetic predisposition to obesity is associated with insulin secretion in Chinese adults: The Cardiometabolic Risk in Chinese (CRC) study.

AIMS: The etiological role of obesity in determining diabetes risk among Asians may be different from that among Caucasians. The current study aimed to investigate the association between genetic predisposition to obesity and measures of insulin secretion and resistance in a large Chinese cohort. METHODS: Study samples were from a community-based health examination survey in central China. A total of 2058 subjects with available biomarkers levels were included in the present study. A genetic risk score (GRS) of obesity was derived on the basis of thirteen Asian-specific body mass index (BMI)-associated variants. RESULTS: High obesity GRS was significantly associated with increased homeostasis model assessment (HOMA)-B score (ß=7.309; P=0.001) but not related to measures of insulin resistance. Adjustment for age, sex, BMI, and levels of lipids did not appreciably change the results. In addition, we found significant interactions between the obesity GRS and measures of body fat distribution including waist circumference (WC; P for interaction=0.004) and neck circumference (NC; P for interaction=0.014) on HOMA-B score. CONCLUSIONS: Our results suggest that genetic predisposition to obesity may affect beta cell function in Chinese; and body fat distribution may modify the genetic effects.

The CDKAL1 gene is associated with impaired insulin secretion and glucose-related traits: the Cardiometabolic Risk in Chinese (CRC) study.

OBJECTIVE: Insulin secretion and insulin resistance, which affect metabolic homoeostasis, each have a significant genetic component. Cyclin- dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) rs10946398, a novel body mass index (BMI)-associated locus specifically in the Asian population, may impair insulin secretion and may be associated with insulin resistance and type 2 diabetes. Our objective was to investigate the impact of the rs10946398 polymorphism of CDKAL1 on insulin secretion, insulin resistance and glucose-related traits in the Chinese population. SUBJECTS AND METHODS: The study samples were based on a community-based health examination survey conducted in central China. Indices of insulin resistance and insulin secretion were derived from fasting glucose measurements and oral glucose tolerance tests (OGTTs). Using multivariate linear regression models, the relationships between the rs10946398 polymorphism of CDKAL1 and insulin secretion, insulin resistance and quantitative glucose-related traits were investigated in 2313 participants. RESULTS: The CDKAL1 rs10946398 C allele showed a significant association with decreased insulin secretion (ß = -0·05, P < 0·0005), but not with insulin resistance (ß = 0·02, P = 0·08). We also found that the CDKAL1 rs10946398 C allele was significantly associated with glucose-related traits (fasting glucose, fasting insulin, 2-h glucose and HbA1c). There was no significant relationship between rs10946398 and other metabolic traits. CONCLUSIONS: rs10946398 of CDKAL1 was associated with markers of impaired insulin secretion. It is reasonable to infer that the relationship between CDKAL1 and metabolic diseases is mediated by its effect on glucose-related traits.

[Porphyrins with different electron groups: spectral and DFT study].

UV-Vis absorption spectra and electrochemical properties of 5-(o-hydroxyphenyl)-10, 15, 20-tri-(p-phenyl)porphyrin (TPPOH) and 5-(o-hydroxyphenyl)-10, 15, 20-tri-(p-methoxyphenyl) porphyrin [(p-OCH3)TPPOH] with different electron groups were investigated by experiments and density functional theory (DFT). Due to the introduction of para-methoxyl group (-OCH3), obvious red shift of 3 nm in the maximum absorbance of the UV-Vis spectra, negative shift in redox potential of (p-OCH3)TPPOH, and the decrease (0.06 eV) in the energy gap (DE) of the frontier highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) (of (p-OCH3)TPPOH occurred as compared to those of TPPOH. The results are due to that electron donating groups of -OCH3 increase the electron density of porphyrin ring in (p-OCH3)TPPOH. Electron distributions of the frontier orbital calculated by DFT showed that the increase in the energy levels of HOMO and LUMO, while the decrease of 0.05 eV in the energy gap. The agreement between experimental result and theoretical value and the further illustration of the mechanism for the spectral change and electrochemical properties provide important bases for the design and application of the porphyrin derivatives with different electron groups.

Hemoglobin A1c levels and aortic arterial stiffness: the Cardiometabolic Risk in Chinese (CRC) study.

OBJECTIVE: The American Diabetes Association (ADA) recently published new clinical guidelines in which hemoglobin A1c (HbA1c) was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT). RESEARCH DESIGN AND METHODS: The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV) and HbA1c were measured in 5,098 men and women. RESULTS: After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend <0.0001). The associations remained significant after further adjustment for blood pressure, heart rate, and lipids (P = 0.004), and the difference in cfPWV between the highest and the lowest quintiles of HbA1c was 0.31 m/s. Fasting glucose and 2 h OGTT were not associated with cfPWV in the multivariate analyses. HbA1c showed additive effects with fasting glucose or 2 h OGTT on cfPWV. In addition, age and blood pressure significantly modified the associations between HbA1c and cfPWV (P for interactions <0.0001 for age; and  = 0.019 for blood pressure). The associations were stronger in subjects who were older (≥60 y; P for trend = 0.004) and had higher blood pressure (≥120 [systolic blood pressure]/80 mmHg [diastolic blood pressure]; P for trend = 0.028) than those who were younger and had lower blood pressure (P for trend >0.05). CONCLUSIONS: HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.