However, studies on bone biochemical markers in T2DM have shown conflicting results, with the inhib- ition of bone formation being reported in most cases [7–9]; a recent survey indicated that there was no differ- ence in bone turnover between Iranian postmenopausal women with and those without diabetes . HbA1c is a stable marker that can characterizes dysglycemia more efficiently than fasting glucose in terms of long-term glucose regulation, Puar TH et al. noted that tight glycemic control (when HbA1c < 7%) was closely related with a greater risk of hip fracture in individuals being treated for T2DM ; in contrary, Schwartz et al. found no increase in the fall risk of patients with stand- ard glydemic control . However, little research has focused on the association between the level of HbA1c and bone biochemical markers. And given the large heterogeneity of these studies, we conducted these experiments to identify the differences between T2DM patients and controls and formulated the following hypothesis: glycosylated hemoglobin A1c levels affect the level of bone biochemical markers.
American Diabetes Association (ADA) had adopted the use of Glycosylated Hemoglobin A1c (HbA1c) measure- ments as a diagnostic test for diabetes. 24 HbA1c is a marker for chronic glycemic exposure which identi ﬁ es average levels of blood glucose over a duration of 2 to 3 months. 24,26 Measurements of HbA1c levels retain multi- ple advantages compared to fasting plasma glucose determination. 27 These advantages include the feasibility and convenience of the analysis since fasting is not required along with reduced sensitivity to acute changes in dietary habits or lifestyle factors. 24,26 In addition, HbA1c levels are not affected by diurnal variations in blood glucose levels and are less sensitive to acute glyce- mic ﬂ uctuations which may result from certain drug treat- ments that cancer patients could be receiving and known to adversely affect fasting glucose levels. 27 Findings from our study revealed that most breast cancer patients in this series were prediabetic with no previous diagnosis of diabetes. This is of particular interest as earlier studies showed that many diabetes cases may remain undiagnosed until a diagnosis of breast cancer is made. 28 In agreement to this ﬁ nding, Erickson et al indicated that among breast cancer patients who were screened for HbA1c and had levels of ≥ 7.0%, less than half reported diabetes. 8 These ﬁ ndings are alarming taking into consideration the nega- tive impact of hyperglycemia on presentation and prog- nosis of breast cancer patients. Prediabetes is associated with high risk of developing diabetes. 29 Earlier evidence indicated that microvascular and macrovascular changes commonly associated with diabetes actually begin during prediabetic stage. 29 Prediabetes is associated with increased risk of various types of tumors including breast, gastric, colorectal, pancreatic, liver, and endometrial cancers. 30,31 In addition, breast cancer patients who were prediabetic are more vulnerable for early detection of breast cancer as the risk of the disease is increased during prediabetes phase. 16,32
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HbA1c: Hemoglobin A1c; eGFR: Estimated glomerular filtration rate; FPG: Fasting plasma glucose; DN: Diabetic nephropathy; ESRD: End-stage renal disease; T2DM: Type 2 diabetes mellitus; DCCT-EDIC: Diabetes control and complications trial-epidemiology of diabetes interventions and complications; ADA: American Diabetes Association; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; CHD: Coronary heart disease; BMI: Body mass index; BP: Blood pressure; TC: Total cholesterol; TG: Triglycerides; LDL-c: Low-density lipoprotein cholesterol; HDL-c: High-density lipoprotein cholesterol; OGTT: Oral glucose tolerance test; NHM: Normal glucose metabolism; SDs: Standard deviations; ACEIs: Angiotensin converting enzyme inhibitors; ARBs: Angiotensin receptor blockers;
Aim: To develop and validate a model, which combines traditional risk factors and glyco- sylated hemoglobin A1c (HbA1c) for predicting the risk of type 2 diabetes (T2DM). Materials and Methods: This is a historical cohort study from a collected database, which included 8419 males and 7034 females without diabetes at baseline with a median follow-up of 5.8-years and 5.1-years, respectively. Multivariate cox regression analysis was used to select signi ﬁ cant prognostic factors of T2DM. Two nomograms were con- structed to predict the 5-year incidence of T2DM based on traditional risk factors (Model 1) and traditional risk factors plus HbA1c (Model 2). C-index, calibration curve, and time-dependent receiver-operating characteristic (ROC) curve were conducted in the training sets and validation sets.
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The underlying hypothesis of the current results might consisted in that the high levels of HbA1c were not only associated with the long-term disorder of glycolipid me- tabolism but also connected with low-grade systematic inflammation and atherosclerotic plaques progress . Our data might supported this hypothesis because we found that higher levels of HbA1c in the population studied were clearly associated with the adverse baseline characteristics such as higher cardiovascular risk profile and higher inflammatory biomarkers such as hs-CRP, leukocyte counts, fibrinogen, D-dimer, uric acid and so on. Our data were also in agreement with previous evidence Table 3 Unadjusted and adjusted predictive value of serum hemoglobin A1C levels for 12-month total outcome
potential to be used as a diagnostic criterion for T2DM in Chinese adults , combining use of the measure- ment with FPG has two additional advantages. Firstly, genetic variants of hemoglobin (e.g. sickle cell trait, HbS trait, HbC trait, etc.) and some medical conditions that Table 2 Performance of the optimal HbA 1c cut-points in participants by demographic and clinical characteristics
BMI: Body mass index; DBP: Diastolic blood pressure; DN: Diabetic nephropathy; ELISA: Enzyme-linked immunosorbent assay; FPG: Fasting plasma glucose; HbA1c: Glycosylated hemoglobin A1c; HDL-C: High-density lipoprotein cholesterol; HS-CRP: High-sensitivity C-reactive protein; IL- 10: Interleukin-10; IL-19: Interleukin-19; LDL-C: Low-density lipoprotein cholesterol; SBP: Systolic blood pressure; T2DM: Type 2 diabetes mellitus; TC: Total cholesterol; Th2: T-helper2; UAE: Urinary albumin excretion
Well-documented evidence suggests that step counter use decreases blood pressure, lipid profiles and improves the quality of life in patients with T2D ; while studies on step counter use for improving glycemic control in pa- tients with T2D give conflicting results [15,19]. Although Bravata et al.  argued that step counter use was not associated with a decreased fasting serum glucose concen- tration, its association with chronic glycemic control, as assessed by glycosylated hemoglobin A1c (HbA1c), remains unknown, which is considered to be the mainstay of T2D management.
Clinical studies on the minor hemoglobins (hemoglobin A1a-c) have suggested that a novel adduct may form in people abusing alcohol. Such patients were found to have an elevated concentration of minor hemoglobins, but normal or subnormal amounts of glycosylated hemoglobin (hemoglobin A1c) as determined by radioimmunoassay, Acetaldehyde, a reactive metabolite of ethanol, was postulated to form adducts with hemoglobin A that change its chromatographic properties. At physiological concentrations, acetaldehyde was found to form adducts with hemoglobin that were stable to extensive dialysis for several days. The amount of hemoglobin adducts formed were a function of the concentration and number of exposures to acetaldehyde. The reaction of acetaldehyde with hemoglobin A produced chromatographic variants, some of which migrated in the hemoglobin A1a-c region. Analysis of stable acetaldehyde-hemoglobin adducts demonstrated that valine, lysine, and tyrosine residues of globin were sites of reaction. The acetaldehyde-modified amino acid residues appear to exist in interconvertible conformations, only one of which is reducible by sodium borohydride. The amount of these adducts was found to be
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After completion of each wave, the PFs screened medical records of diabetic patients between 50 and 84 years of age to identify at least 30 patients with two estimated glomerular filtration rates (eGFR) <60, at least 3 months apart for the next phase of abstraction. If 30 patients meeting these criteria could not be identified, PFs were instructed to search the records of patients between 50 and 84 years of age with a diagnosis of hypertension. If 30 patients still could not be identified, PFs were instructed to identify patients already diagnosed with CKD. The PFs then abstracted the medical records of patients who had evidence of CKD to collect information relevant to prac- tice performance during the specified time periods of interest. Data on the following were abstracted for every visit during the qualifying time period: 1) CKD diagnosis defined as an eGFR staying below 60 for more than 3 months; 2) A1c measurement at least annually, 3) LDL cholesterol measurement at least annually, 4) microalbu- min measurement at least annually, 5) Hgb measurement annually if eGFR <45, 6) ACEI or ARB initiation, 7) dis- continuation of NSAIDS, 8) vitamin D measurement and/ or initiation of vitamin D supplements if eGFR <45, and 9) referral to a nephrologist for any eGFR <30. We also examined changes in LDL, A1c, and the mean of the last three diastolic (DBP) and systolic blood pressures (SBP) before and after the intervention.
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This cross sectional study was conducted among diabetic outpatients in Jimma University Specialized Hospital from 1 May to 31 July 2012. It was aimed to assess the glycemic control status of diabetic patients using glycated hemoglobin test and to determine risk of developing diabetic complication. The hospital is located in Jimma town, Oromia National Regional State at 353 km to the southwestern of Addis Ababa, the capital of Ethiopia. The hospital has 450 beds and is a teaching hospital that gives service to southwestern part of Oromia, part of south- ern people nations and nationalities, as well as Gambella regions of Ethiopia. The hospital has separate chronic ill- ness referral clinic in which diabetic patients are regularly monitored every Mondays and Tuesdays of the week.
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of glycation (otherwise the slopes of both lines would have to be different). Possible mechanisms responsible for such an increase include patients’ susceptibility to oxidative stress and an association of hyperglycemia with free- radical-mediated lipid peroxidation  or the existence of high and low hemoglobin glycation phenotypes [28,29]. On the other hand, some studies have indicated that the life span of erythrocytes is independent of glycemic control or even that it is longer in patients with poorer control [18,30,31], implying that the mean glycation rate is not cor- related or that it is negatively correlated with glycemic control.
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DISCUSSION: In diabetes the increased blood sugar levels might be due to either insulin resistance of the body cells or decreased secretion of insulin from β-cells manifested in the decreased serum insulin levels 29 . The reduction in the serum insulin levels in the STZ-treated rats might be attributed to the reduced secretion of the hormone which might be due to the damage of the β-cells of endocrine pancreas. The STZ selectively destroy the pancreatic cells and induce hyperglycemia. The blood glucose level of GPK extract fed animals was significantly reduced. The highest decrease was recorded in the 400 mg kg -1 GPK and STZ group. In addition, during diabetes the excess glucose present in circulation reacts with hemoglobin to form glycosylated hemoglobin. These findings are in agreement with our studies, in which there was no significant changes observed in total hemoglobin but the glycosylated hemoglobin was significantly higher in diabetic rats. Administrations of GPK extract restored to normal the total hemoglobin and HBA1C in diabetic rats by reducing the glucose levels.
ABI: ankle-brachial index; ACR: albumin-to-creatinine ratio; ADA: American Diabetes Association; A1C: hemoglobin A1C; AHA/ACC: American Heart Association/American College of Cardiology; AHI: apnea hypopnea index; AMI: acute myocardial infarct; ARR: absolute risk reduction; ASCVD: athero- sclerotic cardiovascular disease; CAC: coronary artery calcium score; CHD: coronary heart disease; CMIT: carotid intima-media thickness; CNHSS: China National HbA1c Surveillance System; CI: confidence interval; CRP: C-reactive protein; CV: cardiovascular; CVD: cardiovascular disease; CKD: chronic kidney disease; EBCT: electron-beam computed tomography; ECG: eletrocardiogram; ED: erectile dysfunction; FMD: flow mediated dilation; FPG: fasting plasma glucose; FRS: framingham risk score; GFR: glomerular filtration rate; HDLc: high density lipoprotein; HR: hazard ratio; hs-CRP: high sensitivity c-reactive protein; IL-6: interleukin 6; ICAM: intercellular adhesion molecule; LDL-c: low density cholesterol; MDCT: multi-detector computed tomography; MetS: metabolic syndrome; MPI: adenosine-stress myocardial perfusion imaging; NAFLD: non-alcoholic fatty liver disease; NCEP-ATP III: National Cholesterol Education Program-Adult Treatment Panel III; NHANES III: National Health and Nutrition Examination Survey; OR: odds-ratio; OSA: sleep apnea; PAI-1: plasminogen activator inhibitor-1; ROC: receiver operating characteristic; RR: relative risk; SBP: systolic blood pressure; T1DM: type 1 diabetes; T2DM: type 2 diabetes; VEGF: vascular endothelial growth factor; UK: United Kingdom; UKPDS-RE: United Kingdom Prospective Diabetes Study Risk Engine; VCAM: vascular cell adhesion molecule; WHO: World health Organization.
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less preventive care and guideline adherence in patients with greater comorbidity, and others predict more care due to increased visits and provider contacts . A recent model by Piette and Kerr shifts this concept, arguing that rather than the amount of comorbidity, it is the nature of the specific comorbidities and their rela- tionship to the guideline-based tasks that predicts care delivery [14,15]. The model predicts higher quality when the goals of care for two conditions, such as RA and dia- betes, align or are “ concordant ” , and lower quality when the goals of care for two conditions are “ discordant. ” We hypothesized that providers would consider glycemic control unrelated to the management of RA (goals are discordant), and that active, symptomatic RA disease would in turn lessen attention to diabetes A1c testing. This predicts decreased A1c testing in diabetes patients when RA is present. In contrast, given the heightened cardiovascular risks associated with both RA and dia- betes, we hypothesized that lipid management would be a “ concordant ” preventive goal in patients with both con- ditions, predicting increased lipid testing in diabetes patients when RA was also present.
To investigate the effect of methanolic root extract (MREt) of Rauwolfia serpentina on hyperglycemic, haematinic and antioxidative dysfunction associated with alloxan-induced diabetes. Mice were divided into normal and alloxan-induced diabetic groups, the second group was sub-divided into three MREt (10, 30 & 60mg/kg) treated test groups and three diabetic (distilled water 1ml/kg), negative (0.05% dimethyl sulphoxide 1ml/kg) and positive (glibenclamide 5mg/kg) control groups. Each treatment was done orally for 14 days. The MREt significantly reduced blood glucose level by improving the body weights, glycosylated hemoglobin (HbA1c) to total hemoglobin (Hb) ratio, red blood cell (RBC) & white blood cell (WBC) counts, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) in test groups. Beside this, extract decreases the percent inhibition of catalase (CAT) & superoxide dismutase (SOD) enzymes and restores the liver function by recovering the total protein concentration and normalizing the levels of alanine transaminase (ALT), aspartate transaminase (AST) & alkaline phosphatase (ALP) in test mice. Therefore, MREt ameliorates hyperglycemic, haematinic and antioxidant status in alloxan-induced diabetic mice. Further work is still required to find out the active principle in same extract involved in antidiabetic activity.
The aqueous leaf extract of Passiflora edulis (P.edulis) Sims were investigated for its anti-diabetic effect in Wistar albino rats after induction of diabetes (150 mg/kg, of alloxan, i.p.). Aqueous extract of P.edulis (AEPE) at a dose of 200 mg/kg, p.o was administered as single dose per day to diabetes-induced rats for 30 days. The effect of AEPE leaf extract on blood glucose, insulin, hemoglobin and glycosylated hemoglobin, serum lipid profile, liver glycogen and protein were measured in the diabetic rats. AEPE elicited significant reduction of blood glucose, glycosylated hemoglobin, lipid parameters and serum enzymes and significantly increased plasma insulin, hemoglobin and HDL level. P.edulis also caused significant increases in liver protein, glycogen and normalize the carbohydrate metabolizing enzymes. From the above results, it is concluded that P.edulis possesses significant anti-diabetic effects in alloxan-induced diabetic rats.
Type 2 diabetes mellitus (T2DM) is a pressing health issue that threatens global health and the productivity of populations worldwide. Despite its long-recognized role in diabetes management, glycated hemoglobin (HbA1c) only received WHO endorsement as a T2DM diagnostic tool in 2011. Although conventional plasma- speciﬁc tests have long been utilized to diagnose T2DM, the public should be informed that plasma-speciﬁc tests are not markedly better than HbA1c tests, particularly in terms of variability and convenience for diagnosing diabetes. In the midst of the debates associated with establishing HbA1c as the preeminent diabetes diagnostic tool, unceasing efforts to standardize HbA1c tests have played an integral part in achieving more efﬁcient com- munication from laboratory to clinical practice and thus better diabetes care. This review discusses the current status of HbA1c tests in the diagnosis, prevention, treatment and management of T2DM across the globe, focusing on increasing the recognition of glycated hemoglobin variants with effective utilization of different HbA1c methods, updating the current status of HbA1c standardization programs, tapping into the potential of POC analyzers to establish a cost-effective HbA1c test for diabetes care, and inspiring the advancement of HbA1c biosensors for future clinical usage.
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Table 1 shows the characteristics of the participants at admission to the study. The weeks gestation at deter- mination of HbA1c were 12.3 ± 1.6, 20.1 ± 3.6 and 30.4 ± 2.4 for T1, T2 and T3 groups, respectively. Maternal age was significantly higher in the T1 group than the T2 and T3 groups; however, pregestational BMI was similar in all three groups. Maternal hemoglobin was signifi- cantly higher in the T1 group (13.7 ± 1.1 g/dL) than the T2 (13.2 ± 0.96) and T3 groups (13. ± 1.01 g/dL). No sta- tistically significant difference in glucose values obtained from the 75 g-2 h OGTT were observed for the T1 group in comparison to the T2 and T3 groups. The glu- cose values in OGTT were significantly higher in the T3 group than the T2 group.
monotherapy, HbA1c had to be 7.0%–10.0% at screening; for patients treated with an additional medication, A1c had to be 6.5%–9.0%. Patients taking antidiabetic therapy in addition to metformin were instructed to stop the medication and then underwent a 6-week washout period that included an open- label placebo run-in phase in the last 2 weeks. For patients taking metformin monotherapy at enrolment, only the 2-week run-in phase was required. All eligible patients continued their usual dose of metformin and were then randomized to treatment with either linagliptin 5 mg once daily or placebo for 24 weeks. The primary endpoint was the change from baseline HbA1c, adjusted for baseline HbA1c and the use of monotherapy versus combination therapy at enrolment, after 24 weeks of treatment. At the end of the study, lina- gliptin reduced the mean HbA1c level by 0.49%, whereas HbA1c in the placebo group rose by 0.15% (P , 0.0001). The placebo-corrected reduction in HbA1c was 0.64%. Linagliptin also led to significant reductions versus placebo in both fasting plasma glucose and postprandial plasma glucose (P , 0.0001, see Table 2).
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