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A Two-Step Screening, Measurement of HbA1c in Association with FPG, May Be Useful in Predicting Diabetes  [PDF]
Kyoko Nomura, Kazuo Inoue, Kimihiko Akimoto
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036309
Abstract: Backgrounds We compared the usefulness of fasting plasma glucose (FPG), or hemoglobin A1c (HbA1c), or both in predicting type 2 diabetes. Methods This retrospective cohort study investigated 9,322 Japanese adults (4,786 men and 4,536 women), aged 19–69 yrs, free of diabetes at baseline. Usefulness was assessed by predictive values (PV), sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) maximised under the best cut-off point. Results During the average 6 years of follow-up, 221 men (4.6%) and 92 women (2%) developed diabetes. The best cut-off points for FPG (i.e., 5.67 mmol/l for men and 5.5 mmol/l for women) gave excellent AUROC, and the highest positive PV (13% for men and 9% for women) in predicting diabetes. In high risk subjects with FPG 6.1–6.9 mmol/l, 119 men (26.8%) and 39 women (28.3%) developed diabetes. Under the best cut-off points of FPG 6.39 mmol/l and A1c 5.8, AUROC and positive PV for FPG slightly decreased indicating FPG became less useful and were statistically indistinguishable from those for HbA1c in men. In fact, HbA1c was the most useful in women: HbA1c of 6.0% gave the highest positive likelihood ratio of 2.74 and larger AUROC than did FPG. Although AUROC for HbA1c was acceptable and indistinguishable from that for the combined use, HbA1c had higher specificity and positive LR than did the combined use. Conclusions This study demonstrated that FPG was the most useful to predict diabetes in the general population. However, in subjects with FPG 6.1–6.9 mmol/l, FPG became less useful and diagnostic performance of FPG was indistinguishable from that of HbA1c in men whereas HbA1c was the most useful in women. Thus, a two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.
HbA1c、GSP和FPG检测对2型糖尿病的临床价值  [PDF]
中国热带医学 , 2015,
Abstract: 目的探讨糖化血红蛋白(Glycosylatedhemoglobin,HbA1c)、糖化血清蛋白(Glycosylatedserumprotein,GSP)及空腹血糖(FPG)的检测对糖尿病(DM)诊断、治疗及控制管理的临床价值。方法选择261例经确诊的2型糖尿病患者和62例健康体检者,以酶法分别检测HbA1c、GSP、FPG含量,并进行比较分析。结果在261例2型糖尿病患者中,HbA1c、GSP、FPG的升高率分别为54.0%(141/261)、60.9%(159/261)和93.5%(244/261),差异均具有统计学意义(P<0.01)。HbA1c、GSP、FPG平均含量分别(7.6±1.3)%、(270.4±38.8)μmol/L、(10.5±2.0)mmol/L;62例健康体检者HbA1c、GSP、FPG含量分别为(4.8±1.2)%、(179.2±57.0)μmol/L和(4.8±1.2)mmol/L,2型糖尿病患者和62例健康体检者比较,差异有统计学意义(P<0.01)。结论在2型糖尿病患者中,FPG阳性率最高,提示FPG为检测即时血糖,受到影响因素多,难以代表患者在管理治疗过程中真实血糖水平。因此,如能联合HbA1c和GS检测,对糖尿病评价更有意义。
Evaluation for Fasting and 2-hour Glucose and HbA1c for Diagnosing Diabetes Based on Prevalence of Retinopathy in a Chinese Population  [PDF]
Zhong Xin, Ming-Xia Yuan, Hong-Xing Li, Lin Hua, Jian-Ping Feng, Jing Shi, Xiao-Rong Zhu, Xi Cao, Jin-Kui Yang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040610
Abstract: Background The glycemic thresholds for diabetes diagnosis have long been at the forefront of discussion. However, no information about glycemic cutoff points has been made available for the Chinese population. The aim of the present study was to examine the association of fasting plasma glucose (FPG), 2-h plasma glucose (2-h PG) and HbA1c levels with diabetic retinopathy (DR) and determine the associated cutoff levels in a Chinese population. Methodology and Principal Findings In a cross-sectional population-based sample of 2551 Chinese (representing a population of 1,660,500 in a Beijing district) between 18–79 years of age, the three glycemic measures were measured in a 75 g oral glucose tolerance test, and DR was assessed by two 45° color digital retinal images. The prevalence of DR increased in the ninth decile of each variable, corresponding to an FPG of ≥7.2 mmol/l, a 2-h PG of ≥10.7 mmol/l, and HbA1c of ≥6.4%, according to the Joinpoint regression method. After excluding individuals receiving antihyperglycemic medication, the prevalence significantly increased at an FPG of ≥6.8 mmol/l, a 2-h PG of ≥12.0 mmol/l, and HbA1c of ≥6.7%. The area under the ROC curve for all three measures showed no significant differences for detecting DR. After excluding individuals receiving antihyperglycemic medication, the three measures also showed no significant differences. Conclusions and Significance A significant increase in retinopathy prevalence occurs among individuals with FPG ≥7.2 mmol/l, 2-h PG ≥10.5 mmol/and HbA1c ≥6.4%; and measuring FPG or HbA1c are equally reliable methods as measuring 2-h PG for the diagnosis of diabetes in the Chinese population.
Association of Serum Uric Acid with 2-Hour Postload Glucose in Chinese with Impaired Fasting Plasma Glucose and/or HbA1c  [PDF]
Hong-Qi Fan, Wei Tang, Zhi-Xiao Wang, Su-Juan Wang, Yue-Hua Qin, Qi Fu, Yuan Gao, Min Sun, Mei Zhang, Hong-Wen Zhou, Tao Yang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067759
Abstract: Objective To examine whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in Chinese with impaired fasting plasma glucose (IFG) and/or HbA1c (IA1C). Research Design and Methods Anthropometric and biochemical examinations, such as SUA concentration, were performed in 3763 individuals from all the villages in Baqiao County, China. A 75-g oral glucose tolerance test (OGTT) was conducted in 1197 Chinese with prediabetes as having IFG (110≤ fasting plasma glucose [FPG] <126 mg/dl and HbA1c <6.5%), IA1C (5.7% ≤ HbA1c <6.5% and FPG <126 mg/dl), or both. Results The present study included 1197 participants with IFG and/or IA1C (mean age 56.5±10.3 years; 50.6% men). In multivariate linear regression, after adjustment for gender, age, smoking and drinking, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), lipid profiles, logarithmic transformed C-reactive protein (log-CRP), estimated glomerular filtration rate (e-GFR), FPG and HbA1c, with a 1-mg/dl increment of SUA, 2-h PG increased by 5.04±0.72 (P<0.001), 3.06±1.08 (P = 0.001), 5.40±1.26 (P<0.001), and 2.34±2.16 mg/dl (P = 0.056) in all participants, in participants with normal glucose tolerance (NGT), with impaired glucose tolerance (IGT), and with 2-h newly diagnosed diabetes (2-h NDM, with 2-h PG ≥200 mg/dl), respectively. In both men and women, 2-h PG increased progressively and significantly from the lower to the upper SUA tertiles (P<0.001). Moreover, in multivariate logistic regression, 1-standard deviation (SD; 1.53 mg/dl) increment of SUA was significantly associated with a 36% higher risk for 2-h NDM (Odds ratio [CI 95%]: 1.36 [1.09–1.99]; P = 0.03). Conclusions SUA is significantly associated with 2-h PG in Chinese with IFG and/or IA1C.
HbA1c of 6.5% to Diagnose Diabetes Mellitus?—?Does It Work for Us??—?The Bellville South Africa Study  [PDF]
Annalise E. Zemlin, Tandi E. Matsha, Mogamat S. Hassan, Rajiv T. Erasmus
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022558
Abstract: Background HbA1c has been the gold standard for glycaemic control follow-up for decades. In 2009, a level of 6.5% (48 mmol/mol) was proposed as diagnostic for diabetes. We test this cut-off in our community. Methods Participants (946) from a community-based study were screened for diabetes using either a fasting blood glucose or oral glucose tolerance test (OFTT). The HbA1c cut-off of 6.5% was tested for each group. A receiver operator characteristic (ROC) curve for both groups was generated to establish an optimal cut-off. Results Our study included 224 (23.7%) males and 722 (76.3%) females. Using fasting blood glucose alone, 117 (14%) were diagnosed with diabetes ?50% had an HbA1c value of ≥6.5% (48 mmol/mol). Using an OGTT, 147 (18%) were diagnosed with diabetes ?46% had an HbA1c value of ≥6.5% (48 mmol/mol). ROC curves found a level of 6.1% (43 mmol/mol) to be optimal in both groups (AUC 0.85 and 0.82 respectively). The sensitivities were 80% and 75% and the specificities 77% and 78% respectively. Conclusions A cut off of 6.5% (48 mmol/mol) is a good diagnostic tool with its high specificity; however the low sensitivity limits its use. We found a level of 6.1% (43 mmol/mol) to be optimal. This emphasizes the need for evidenced based values to be established in various population groups.
The Relationship Between Fasting, Postprandial Glucose Levels and HbA1c in Patients with Type 1 Diabetes  [PDF]
Davut Ak?n,Timu?in ?il,Yekta Tüzün,Deniz G?kalp
Dicle Medical Journal , 2008,
Abstract: Several previous studies investigated the relationship between plasma glucose and HbA1c. We aimed to evaluate the relationship between HbA(1c) and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels in type 1 diabetic subjects 86 Type 1 diabetic patients admitted to our department were included. FPG, PPG and HbA1c values were recorded. Pearson’s correlation was used between FPG, PPG and HbA1c.The mean age was 26.8±8.4 years, and mean duration of diabetes was 6.9±4.2 years. The means of FPG, PPG, and HbA1c were 230±109 mg/dl, 299±123 mg/dl ve 9,8±2,8%, respectively. A HbA1c level < 7.0% was obtained in 13 (15.1%) patients. Pearson's correlation coefficient for HbA1c and FPG, and PPG 0.26 (p<0,05), and 0.46 (P<0.01), respectively. Correlation was higher in males.The correlation coefficient of patients with type 1 diabetes for HbA1c and PPG is lower than those of HbA1c and FPG. Therefore, we suggest that using PPG in diabetes management.
Evaluation of Glycated Hemoglobin (HbA1c) for Diagnosing Type 2 Diabetes and Prediabetes among Palestinian Arab Population  [PDF]
Akram T. Kharroubi, Hisham M. Darwish, Ahmad I. Abu Al-Halaweh, Umaiyeh M. Khammash
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088123
Abstract: The purpose of the study is to compare the potential of HbA1c to diagnose diabetes among Palestinian Arabs compared to fasting plasma glucose (FPG). A cross-sectional sample of 1370 Palestinian men (468) and women (902) without known diabetes and above the age of 30 years were recruited. Whole blood was used to estimate HbA1c and plasma for FPG and total lipid profile. Fasting plasma glucose was used as a reference to diagnose diabetes (≥ 126 mg/dL) and prediabetes (100–125 mg/dL). The area under the receiver operating characteristic curve (AUC) for HbA1c was 81.9% to diagnose diabetes and 63.9% for prediabetes. The agreement between HbA1c and diabetes as diagnosed by FPG was moderate (? = 0.498) and low with prediabetes (? = 0.142). The optimal cut-off value for HbA1c to diagnose diabetes was ≥ 6.3% (45 mmol/mol). The sensitivity, specificity and the discriminant ability were 65.6% (53.1–76.3%), 94.5% (93.1–95.6%), 80.0% (72.8–87.3%), respectively. However, using cut-off value of ≥ 6.5% (48 mmol/mol) improved specificity. At this cut-off value, the sensitivity, specificity and the discriminant ability were 57.4% (44.9–69.0%), 97.1% (96.0–97.9%) and 77.3% (71.0–83.5%). For diagnosing prediabetes with HbA1c between 5.7–6.4% (39–46 mmol/mol), the sensitivity, specificity and the discriminant ability were 62.7% (57.1–67.9%), 56.3% (53.1–59.4%) and 59.5% (56.3–62.5%), respectively. HbA1c at cut-off value of ≥ 6.5% (48 mmol/mol) by itself diagnosed 5.3% and 48.3% as having diabetes and prediabetes compared to 4.5% and 24.2% using FPG, respectively. Mean HbA1c and FPG increase significantly with increasing body mass index. In conclusion, the ROC curves showed HbA1c could be used for diagnosing diabetes when compared to FPG but not for prediabetes in Palestinians Arabs even though only about 50% of the diabetic subjects were identified by the both HbA1c and FPG.
Use of HbA1c in the Identification of Patients with Hyperglycaemia Caused by a Glucokinase Mutation: Observational Case Control Studies  [PDF]
Anna M. Steele, Kirsty J. Wensley, Sian Ellard, Rinki Murphy, Maggie Shepherd, Kevin Colclough, Andrew T. Hattersley, Beverley M. Shields
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065326
Abstract: Aims HaemoglobinA1c (HbA1c) is recommended for diabetes diagnosis but fasting plasma glucose (FPG) has been useful for identifying patients with glucokinase (GCK) mutations which cause lifelong persistent fasting hyperglycaemia. We aimed to derive age-related HbA1c reference ranges for these patients to determine how well HbA1c can discriminate patients with a GCK mutation from unaffected family members and young-onset type 1 (T1D) and type 2 diabetes (T2D) and to investigate the proportion of GCK mutation carriers diagnosed with diabetes using HbA1c and/or FPG diagnostic criteria. Methods Individuals with inactivating GCK mutations (n = 129), familial controls (n = 100), T1D (n = 278) and T2D (n = 319) aged ≥18years were recruited. Receiver Operating Characteristic (ROC) analysis determined effectiveness of HbA1c and FPG to discriminate between groups. Results HbA1c reference ranges in subjects with GCK mutations were: 38–56 mmol/mol (5.6–7.3%) if aged ≤40years; 41–60 mmol/mol (5.9–7.6%) if >40years. All patients (123/123) with a GCK mutation were above the lower limit of the HbA1c age-appropriate reference ranges. 69% (31/99) of controls were below these lower limits. HbA1c was also effective in discriminating those with a GCK mutation from those with T1D/T2D. Using the upper limit of the age-appropriate reference ranges to discriminate those with a mutation from those with T1D/T2D correctly identified 97% of subjects with a mutation. The majority (438/597 (73%)) with other types of young-onset diabetes had an HbA1c above the upper limit of the age-appropriate GCK reference range. HbA1c ≥48 mmol/mol classified more people with GCK mutations as having diabetes than FPG ≥7 mmol/l (68% vs. 48%, p = 0.0009). Conclusions Current HbA1c diagnostic criteria increase diabetes diagnosis in patients with a GCK mutation. We have derived age-related HbA1c reference ranges that can be used for discriminating hyperglycaemia likely to be caused by a GCK mutation and aid identification of probands and family members for genetic testing.
Fluctuation between Fasting and 2-H Postload Glucose State Is Associated with Chronic Kidney Disease in Previously Diagnosed Type 2 Diabetes Patients with HbA1c ≥ 7%  [PDF]
Chuan Wang, Jun Song, Zeqiang Ma, Weifang Yang, Chengqiao Li, Xiuping Zhang, Xinguo Hou, Yu Sun, Peng Lin, Kai Liang, Lei Gong, Meijian Wang, Fuqiang Liu, Wenjuan Li, Fei Yan, Junpeng Yang, Lingshu Wang, Meng Tian, Jidong Liu, Ruxing Zhao, Li Chen
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102941
Abstract: Objective To investigate how the glucose variability between fasting and a 2-h postload glucose state (2-h postload plasma glucose [2hPG]-fasting plasma glucose [FPG]) is associated with chronic kidney disease (CKD) in middle-aged and elderly Chinese patients previously diagnosed with type 2 diabetes. Design and Methods This cross-sectional study included 1054 previously diagnosed type 2 diabetes patients who were 40 years of age and older. First, the subjects were divided into two groups based on a glycated hemoglobin (HbA1c) value of 7%. Each group was divided into two subgroups, with or without CKD. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the glomerular filtration rate (GFR). CKD was defined as eGFR<60 mL/min/1.73 m2. Multiple linear regression analysis was used to estimate the association between the 2hPG-FPG and eGFR. The 2hPG-FPG value was divided into four groups increasing in increments of 36 mg/dl (2.0 mmol/L): 0–72, 72–108, 108–144 and ≥144 mg/dl, based on the quartiles of patients with HbA1c levels ≥7%; then, binary logistic regression analysis was used to investigate the association between 2hPG-FPG and the risk of CKD. Results In the patients with HbA1c levels ≥7%, the 2hPG-FPG was significantly associated with decreased eGFR and an increased risk of CKD independent of age, gender, body mass index (BMI), systolic blood pressure (BP), diastolic BP, smoking, and drinking, as well as fasting insulin, cholesterol, triglyceride, and HbA1c levels. The patients with 2hPG-FPG values ≥144 mg/dl showed an increased odds ratio (OR) of 2.640 (P = 0.033). Additionally, HbA1c was associated with an increased risk of CKD in patients with HbA1c values ≥7%. Conclusions The short-term glucose variability expressed by 2hPG-FPG is closely associated with decreased eGFR and an increased risk of CKD in patients with poor glycemic control (HbA1c≥7%).
Characterization of the meningococcal DNA glycosylase Fpg involved in base excision repair
Katrina L Tibballs, Ole Ambur, Kristian Alfsnes, H?vard Homberset, Stephan A Frye, Tonje Davidsen, Tone T?njum
BMC Microbiology , 2009, DOI: 10.1186/1471-2180-9-7
Abstract: The deduced N. meningitidis Fpg amino acid sequence was highly homologous to other Fpg orthologues, with particularly high conservation of functional domains. As for most N. meningitidis DNA repair genes, the fpg gene contained a DNA uptake sequence mediating efficient transformation of DNA. The recombinant N. meningitidis Fpg protein was over-expressed, purified to homogeneity and assessed for enzymatic activity. N. meningitidis Fpg was found to remove 2,6-diamino-4-hydroxy-5-formamidopyrimidine (faPy) lesions and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8oxoG) opposite of C, T and G and to a lesser extent opposite of A. Moreover, the N. meningitidis fpg single mutant was only slightly affected in terms of an increase in the frequency of phase variation as compared to a mismatch repair mutant.Collectively, these findings show that meningococcal Fpg functions are similar to those of prototype Fpg orthologues in other bacterial species.Neisseria meningitidis, or the meningococcus (Mc), exclusively colonizes the oro- and nasopharynx of humans. It resides as a commensal in approximately 10% of healthy individuals [1], but may become virulent, disseminating into the bloodstream and crossing the blood-brain barrier [2]. Mc septicaemia and meningitis are the cause of significant morbidity and mortality worldwide [2].On the mucosal surface of the upper respiratory tract, Mc is exposed to reactive oxygen species (ROS) produced by the immune system through the oxidative burst and by endogenous aerobic metabolism, causing damage to many cellular components, including DNA [3]. Oxidative DNA lesions comprise single- and double strand breaks, abasic (apurinic/apyrimidinic, or AP) sites, and base damages, among which one of the most common is the oxidation product of guanine, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8oxoG). The mutagenic 8oxoG can mispair with adenine during replication and cause G:C → T:A transversions [4]. 2,6-diamino-4-hydroxy-5-formamidopyrimidine (faPy) is another o
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