Aspirin resistance associated with HbA1c and obesity in diabetic patients

INTRODUCTION: Diabetes is known to be a prothrombotic state. Since serotonin uptake plays a role in both platelet activation and depression, we undertook to examine a hypothesis that aspirin resistance (AR) may be associated with both HbA1c and depressive symptoms and to assess other potential determinants of AR in diabetic patients. METHODS: A whole-blood desktop platelet function analyzer (PFA-100) with an epinephrine agonist was used to assess AR among patients with type 2 diabetes. AR was defined as PFA closure times <192 s. Depression symptoms were assessed with the Physicians Health Questionnaire. Patients being treated for type 2 diabetes (N=48) who took aspirin within the past 24 h constituted the study sample. Associations with AR were assessed with the use of the Mann-Whitney test and Fisher's Exact Test as well as with logistic regression models. RESULTS: AR was observed in 11 patients (23%) and was not significantly associated with age, sex, or race. AR was significantly associated with HbA1c > or = 8% (P=.002) and obesity (BMI> or = 30 kg/m(2); P=.01) and borderline associated with having > or = 1 depressive symptom (P=.07). Results were similar after multivariable adjustment in logistic regression models. No statistically significant associations of AR with age, sex, race, plasma glucose, blood pressure, cholesterol, or smoking were observed. CONCLUSION: These data suggest that AR may be of special concern for diabetic patients with poor glucose control and obesity. Whether the PFA-100 or any other practical measure of AR can be used in clinical practice to identify added cardiovascular disease risk and to inform platelet inhibition therapy needs further study.     

Glucose-lowering effect of colestimide is associated with baseline HbA1c in type 2 diabetic patients with hypercholesterolemia

We previously reported that colestimide, an anion exchange resin, improved glycemic control in patients with type 2 diabetes. However, the factors associated with the decrease of HbA1c remain unclear. In present study, we retrospectively compared glycemic control between groups receiving colestimide (n=71), atorvastatin (n=99), pravastatin (n=85), and pitavastatin (n=95) until 3 months after the start of treatment. In the colestimide group, fasting plasma glucose decreased significantly from 169 ± 59 to 138 ± 29 mg/dL after 3 months (P<0.01), and glycated hemoglobin (HbA1c) declined from 8.1 ± 1.0% to 7.4 ± 0.8% (an 8% reduction, P<0.01). Fasting plasma glucose and HbA1c did not change in the pravastatin and pitavastatin groups. On the other hand, both parameters increased significantly in the atorvastatin group. Multivariate analysis revealed that baseline HbA1c was the main determinant of the decrease of HbA1c in the colestimide group while age, sex, BMI, and baseline lipid levels were not correlated with the effect of colestimide treatment. The decrease of HbA1c showed a positive correlation with baseline HbA1c (r=0.60, P<0.0001), and patients with a larger change of HbA1c (>8.4%) displayed a better response to colestimide. In conclusion, since patients with type 2 diabetes often have hyperlipidemia as well, colestimide therapy may have a clinically useful dual action in such patients. Baseline HbA1c has the most important independent influence on the glucose-lowering effect of colestimide.     

Serum HbA1c levels and exercise capacity in diabetic patients.

It is well known that cardiovascular morbidity and mortality are high in diabetic patients. Cardiac involvement is silent and early and these diabetic patients generally complain of chronic fatigue. This study was designed to evaluate the relation between glycemic control and exercise capacity in 330 diabetic patients who have no cardiac symptoms by sustaining dynamic exercise. After a cardiac examination, patients with coronary heart disease, ECG abnormalities, cardiac failure, valvular disease, cerebrovascular disease, peripheral artery disease, anaemia and peripheral neuropathy were excluded. Plasma HbA1c and lipid levels were obtained and a symptom limited exercise test based on "Bruce Protocol" was performed on all patients. Plasma HbA1c levels were significantly increased in smokers and in hypercholesterolemic patients (p<0.001, p=0.006). A moderate correlation between exercise capacity and HbA1c levels, and a weak correlation between duration of diabetes, age, sex, hypertension and plasma lipids were obtained. Multivariant regression analys is revealed that only HbA1c and hypercholesterolemia affected exercise capacity independently (r=-0.54 r=-0.30). In conclusion, poor glycemic control in diabetic patients causes earlier cellular involvement. Because of the high affinity of HbA1c to oxygen, the energy metabolism of the cell is affected, with a clinical correlation between chronic fatigue and worsening exercise capacity.     

Personality as a predictor of HbA1c level in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for around 90% of all cases worldwide. One means to strengthen the prevention and treatment of diabetes is via changes in self-management and lifestyle behaviors. However, lifestyle and personal health behaviors are strongly influenced by personality traits, and thus personality may play a significant role in such aspects as medication compliance, exercise habits, blood glucose monitoring, diet control, and maintenance of an ideal body weight.In this study, we examined whether certain personality traits of patients with T2DM are correlated with higher glycohemoglobin (HbA1c) levels.A total of 214 participants with T2DM were recruited from an outpatient setting. χ² test and logistic regression analyses with 5 models were employed.The OR for the “neuroticism” trait was 3.199 (95% CI = 1.228–8.331, P = .017), and those with this trait were 3.199 times more likely to have higher HbA1c levels than those with the “openness-extraversion” personality trait. This strong relationship between neuroticism and a higher HbA1c level was also evident in models 2, 3, 4, and 5. One-way ANOVA also indicated that the group with the neuroticism personality trait had significantly different mean fasting glucose, HbA1c, triglyceride, and high-density lipoprotein cholesterol levels.We found that a personality characterized by neuroticism is an independent predictor of higher HbA1c level in this study. We also found that people in the pre-contemplation and contemplation stages of exercise have higher HbA1c levels.     

2型糖尿病糖化血红蛋白与血糖波动关系分析

如何准确评价糖尿病的血糖控制状况成为当前的热门话题.糖化血红蛋白(HbA1c)是目前糖尿病筛选、血糖控制、疗效评估的有效检测指标,但其能否真实、全面地反映患者血糖控制情况呢?     

Optimal HbA1c cutoff for detecting diabetic retinopathy

The associations between high glucose levels and diabetic retinopathy have been the basis for the diagnosis of diabetes. We aimed to provide updated data on the relationship between HbA1c and diabetic retinopathy, and to assess the diagnostic accuracy of the proposed HbA1c cutoff for detecting diabetic retinopathy. This cross-sectional study included 3,403 adults from the 2009 to 2010 Ansung Cohort Study. Retinopathy was assessed with single-field nonmydriatic fundus photography and graded according to the International Clinical Diabetic Retinopathy Disease Severity Scale. HbA1c was measured by standardized assay using high performance liquid chromatography. Based on deciles distribution, the prevalence of retinopathy was very low until the HbA1c range of 48–51 mmol/mol (6.5–6.8 %). The optimal HbA1c cutoff for detecting any diabetic retinopathy was 49 mmol/mol (6.6 %), moderate or severer retinopathy was 52 mmol/mol (6.9 %) from receiver operating characteristic curve analysis. The proposed HbA1c threshold of 48 mmol/mol (6.5 %) from American Diabetes Association produced comparable accuracy for identifying both any and moderate/severer retinopathy. This study confirmed that the proposed HbA1c threshold of 48 mmol/mol (6.5 %) allowed the proper detection of diabetic retinopathy. Our data support the judicious use of HbA1c for the diagnosis of diabetes and detecting diabetic retinopathy as well.     

Sex differences in the risk of stroke and HbA1c among diabetic patients

Aims/hypothesis

Sex differences in macrovascular disease, especially in stroke, are observed across studies of epidemiology. We studied a large sample of patients with type 2 diabetes to better understand the relationship between glycaemic control and stroke risk.

Methods

We prospectively investigated the sex-specific association between different levels of HbA_1c and incident stroke risk among 10,876 male and 19,278 female patients with type 2 diabetes.

Results

During a mean follow-up of 6.7 years, 2,949 incident cases of stroke were identified. The multivariable-adjusted HRs of stroke associated with different levels of HbA_1c at baseline (HbA_1c <6.0% [<42 mmol/mol], 6.0–6.9% [42–52 mmol/mol] [reference group], 7.0–7.9% [53–63 mmol/mol], 8.0–8.9% [64–74 mmol/mol], 9.0–9.9% [75–85 mmol/mol] and ≥10.0% [≥86 mmol/mol]) were 0.96 (95% CI 0.80, 1.14), 1.00, 1.04 (0.85, 1.28), 1.11 (0.89, 1.39), 1.10 (0.86, 1.41) and 1.22 (0.92, 1.35) (p for trend?=?0.66) for men, and 1.03 (0.90, 1.18), 1.00, 1.09 (0.94, 1.26), 1.19 (1.00, 1.42), 1.32 (1.09, 1.59) and 1.42 (1.23, 1.65) (p for trend <0.001) for women, respectively. The graded association between HbA_1c during follow-up and stroke risk was observed among women (p for trend?=?0.066). When stratified by race, whether with or without glucose-lowering agents, this graded association of HbA_1c with stroke was still present among women. When stratified by age, the adjusted HRs were significantly higher in women older than 55 years compared with younger women.

Conclusions/interpretation

The current study suggests a graded association between HbA_1c and the risk of stroke among women with type 2 diabetes. Poor control of blood sugar has a stronger effect in diabetic women older than 55 years.     

The value of admission HbA(1c) level in diabetic patients with acute coronary syndrome

Background:

Elevated admission glucose level is a strong predictor of short‐term adverse outcome in patients with acute coronary syndrome (ACS). However, the prognostic value of diabetic control (ie, hemoglobin A_1c levels) in patients with ACS is still undefined.

Hypothesis:

Hemoglobin A_1c level may predict short‐term outcome in patients with ACS.

Methods:

We conducted a retrospective study with prospective follow‐up in 317 diabetic patients with ACS. Patients were stratified into 2 groups based on HbA_1c level, checked within 8 weeks of the index admission (optimal control group, HbA_1c ≤7%; suboptimal control group, HbA_1c >7%). All patients were followed up prospectively for major adverse cardiovascular events (MACE) and mortality for 6 months. Short‐term clinical outcomes were also compared between the 2 study groups.

Results:

In our cohort, 27.4%, 46.4%, and 26.2% patients had unstable angina, non–ST‐segment elevation myocardial infarction, and ST‐segment elevation myocardial infarction, respectively. In‐hospital mortality was similar in both HbA_1c groups (3.37% vs 2.88%, P = 0.803). Six‐month MACE was also similar (26.40% vs 26.47%, P = 0.919). All‐cause mortality, cardiovascular mortality, symptom‐driven revascularization, rehospitalization for angina, and hospitalization for heart failure were also similar in both groups. The hazard ratios for 6‐month MACE and individual endpoints were also similar in both groups.

Conclusions:

This study suggests that HbA_1c levels before admission are not associated with short‐term cardiovascular outcome in diabetic patients subsequently admitted with ACS. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

HbA1c

Non-diagnosed diabetes is a widespread problem in hospitals. Since 2010 the HbA_1c test is recommended for the diagnosis of diabetes mellitus. This test could possibly increase the frequency of the diagnosis of diabetes if used for screening. The test is probably cost-effective. Future studies should test these assumptions.     

Lipid peroxidation,antioxidants, lipid profile,and HbA1c in diabetic patients

Diabetes mellitus is characterized by hyperglycemia together with biochemical changes in glucose, lipid profile, lipid peroxidation, and antioxidants status. This study aims to assess lipid profile, lipid peroxidation, antioxidants, and glycated hemoglobin (HbA1c) in type 1 and type 2 diabetic subjects. Type 1 and type 2 diabetic patients were selected from the subjects attending OPD in Nepalgunj Medical College, Nepal, for medical checkup. Fasting blood sugar (FBS), lipid profile, lipid peroxidation (malondialdehyde), and antioxidants status (reduced glutathione and vitamin E) were estimated in both groups and were compared with healthy controls. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was calculated to assess the cardiovascular risk factors. When type 1 diabetic patients were compared with type 2 diabetic patients, it showed statistically significant increase in the levels of HbA1c, triglycerides (TGs), and high-density lipoprotein cholesterol (HDL-C), whereas statistically significant decreased level was found in malondialdehyde (MDA). FBS, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), vitamin E, and HDL/LDL ratio were not significant. Early diagnosis of dyslipidemia and oxidative stress can be used as a preventive measure for the development of microvascular and macrovascular complications in type 1 and type 2 diabetes mellitus.     

Association of fatty acid profile in plasma lipid fractions with HbA1c in type 2 diabetic patients

The aim of this pilot study has been the comparison of fatty acid profiles of diabetic and healthy subjects in order to evaluate the relationship between fatty acid profiles in plasma lipid fractions and glycated haemoglobin (HbA1c) in type 2 diabetes (T2D) patients. The fatty acid composition of fasting plasma lipid subfractions has been analyzed in patients (n?=?26) diagnosed with T2D and in corresponding control group (n?=?26) of healthy voluntary blood donors. Five subfractions containing phospholipids (PLs), diglycerides (DGs), free fatty acids (FFAs), triglycerides (TGs), and cholesterol esters (CEs) were isolated from plasma samples and separated by thin-layer chromatography. Fatty acid composition of these subfractions was analyzed by GC/FID. Significant changes in fatty acid profiles were found in all lipid fractions from T2D patients in comparison with the control group. HbA1c correlated negatively with delta 9 desaturation (9D) index. Significantly positive correlation of palmitic acid levels and negative correlation of oleic acid levels with HbA1c concentration were found in PL and TG fractions with higher significance in TGs. This pilot study has shown possible associations of HbA1c, common parameter measured in routine laboratories, with lipid metabolism. The strongest correlation was found in plasma TGs, especially in case of palmitic and oleic acids. This is the first report showing that metabolic control assessed by HbA1c is negatively associated with delta 9D index.     

HOMA-S is associated with greater HbA1c reduction with a GLP-1 analogue in patients with type 2 diabetes

Exenatide, a glucagon-like peptide-1 (GLP-1) analogue, is an effective glucoregulator for treating overweight individuals, not at target HbA1 c. This prospective study aimed to determine whether estimates of beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) predict response to Exenatide treatment.Prospective data on 43 type 2 diabetes patients were collected for up to 2.8 years in UK primary care. HOMA-B and HOMA-S were estimated prior to initiating Exenatide, with monitoring of cardio-metabolic risk factors.Mean (SD) age and BMI pre-treatment were 54.1±10.5 years and 35.7±7.5 kg/m2 respectively. HbA1c decreased (mean reduction 0.9%, p=0.04; p for trend=0.01) in 61% of patients. In univariate analyses, HOMA-S as a measure of insulin sensitivity was inversely (β=- 0.41, p 0.009) related to change in HbA1c, with no relation for HOMA-B.In a random effects regression model that included age at baseline, weight, LDL-C, HDL-C and triglycerides, change in HbA1c (β= - 0.14, p<0.001) and HDL-C (β= - 0.52, p=0.011) were independently associated with increasing insulin sensitivity (r2=0.52). Thus patients with greater measured insulin sensitivity achieved greater reduction in HbA1c independent of the factors described above.In logistic regression those in the highest tertile of log-HOMA-S were 45% more likely to have a fall in HbA1c with an odds ratio (OR) of 0.55 (95% CI 0.47-0.66) p<0.0001 (log likelihood ratio for the model χ2=71.6, p<0.0001).Patients with greater measured insulin sensitivity achieve greater reduction in HbA1c with Exenatide. Determination of insulin sensitivity may assist in guiding outcome expectation in overweight patients treated with GLP-1 analogues.     

2型糖尿病患者不同HbA1c水平和骨代谢指标的关系

目的 观察2型糖尿病患者不同HbA1c水平对骨代谢指标骨γ-羧谷氨酸包含蛋白(骨钙素)、Ⅰ型胶原交联羧基端肽(CTX-Ⅰ)、碱性磷酸酶(ALP)的影响.方法 选取2013年10月—2014年1月在哈尔滨医科大学附属第二医院内分泌科住院的120例男性2型糖尿病患者和来自体检中心的40名健康男性作为研究对象.将120例2型糖尿病患者根据HbA1c水平分为为HbA1c≤7％组、HbA1c 7％～ 9％组、HbA1c≥9％组,将40名健康男性作为对照组.采集其年龄、体重指数、病程及血钙、血磷、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶等临床指标,检测血清HbA1c、骨钙素、CTX-Ⅰ、ALP等指标.对4组间HbA1c水平与骨钙素、CTX-Ⅰ、ALP进行相关性和回归分析.结果 与对照组相比,HbA1c≤7％组、HbA1c 7％～9％组及HbA1c≥9％组血清骨钙素水平显著降低(F=7.211,P<0.05),血清ALP、CTX-Ⅰ水平显著升高(F=4.382、809.475,P<0.05);与HbA1c≤7％组相比,HbA1c7％～ 9％组和HbA1c≥9％组血清ALP水平显著降低(P<0.05),血清CTX-Ⅰ水平显著升高(P<0.05);与HbA1c7％～9％组相比,HbA1c≥9％组血清骨钙素水平显著降低(P<0.05),血清CTX-Ⅰ水平显著升高(P<0.05).Spearman相关分析发现,骨钙素与空腹血糖(r=-0.249,P=0.002)、糖化白蛋白(GA,r=-0.321,P=0.000)、HbA1c(r=-0.288,P=0.000)水平呈负相关,ALP、CTX-Ⅰ与空腹血糖(r=0.218、0.321)、GA(r =0.302、0.291)、HbA1c(r =0.321、0.238)水平呈正相关(P均<0.01).进一步经线性回归分析发现,骨钙素水平与GA(β=-0.086,P=0.008)、HbA1c(β=-0.502,P=0.001)呈负相关,CTX-Ⅰ水平与空腹血糖(β=0.042,P =0.003)、GA (β=0.007,P=0.015)、HbA1c(β=0.037,P=0.009)呈正相关.结论 2型糖尿病患者存在骨代谢指标异常,且HbA1 c与骨钙素、CTX-Ⅰ水平相关.     

HbA1c in pregnancy

During pregnancy, the glucose levels vary according to the hormonal changes and the metabolic needs necessary to maintain fetal nutrition but strict glycemic control is essential to minimize the maternal and fetal morbidity and mortality of pregnancies complicated by diabetes. Although considered the “gold standard” for diagnosis, measurement of glucose in the blood is subject to several limitations, many of which are not widely appreciated. Measurement of A1c for diagnosis is appealing as with one number, a total, integrated view of glycemia over time is derived though it has some inherent limitations. Thus, supplementation with HbA1c, as is common outside pregnancy, seems appropriate. Before pregnancy, the target for metabolic control in women with diabetes is HbA1c values near the normal range. However, the upper normal range of HbA1c during normal pregnancy is only sparsely investigated with different methods though recently a number of papers have been published regarding the determination of reference ranges for HbA1c in pregnancy. These changes may have clinical implications for the assessment and management of glycemic control in diabetic pregnancy and calls for establishment of separate reference limits of HbA1c levels in different trimesters as compared to general population.     

Continuous glucose monitoring reduces both hypoglycaemia and HbA1c in hypoglycaemia-prone type 1 diabetic patients treated with a portable pump

AimThis study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and presenting with frequent hypoglycaemic episodes.MethodsThirteen patients with type 1 diabetes (diabetes duration: 25 ± 15 years; CSII duration: 5.5 ± 7.0 years), with more than six recorded capillary blood glucose (CBG) values < 60 mg/dL, according to their metres for the past 14 days, were offered the permanent use of a CGM device (Guardian RT^®, Medtronic) plus ongoing self-monitoring of blood glucose (SMBG) for 12 weeks, followed by a 12-week crossover period of SMBG only, or vice versa. Glucose control, determined by recorded 14-day CBG values < 60 mg/dL and HbA_1c levels, and quality of life according to the Diabetes Quality of Life (DQOL) questionnaire, were assessed at baseline, and after 12- and 24-week follow-ups.ResultsFour patients withdrew from the study during the first period (of whom three were using CGM). In the nine study completers, the number of low CBG values decreased significantly from 13.9 ± 9.2 to 7.6 ± 6.8 (P = 0.011) when patients used CGM, in either the initial or final trial period, while a decrease in HbA_1c from 8.3 ± 0.7 to 7.7 ± 0.6% (P = 0.049) was also observed, in contrast to the absence of any significant differences during the SMBG-only period. DQOL scores were also essentially unaffected.ConclusionThis pilot observational study supports the hypothesis that CGM use can significantly improve overall glucose control while reducing hypoglycaemic episodes in hypoglycaemia-prone type 1 diabetic patients treated by CSII.     

吸烟对冠心病合并糖尿病患者糖化血红蛋白的影响

目的探讨吸烟对冠心病合并糖尿病患者HbA1c水平的影响。方法从北京、上海等7个城市共52家医院心内科2005年6月至9月间冠心病合并糖尿病住院患者中收集有效病例1858例。结果吸烟组HbA1c均值较非吸烟组高（P〈0．01）；HbA1c≥6．5％的比例也高于非吸烟组（P〈0．01）。结论吸烟是HbA1c〉6．5％的冠心病合并糖尿病患者的独立危险因素。应采取积极有效的干预措施降低冠心病合并糖尿病患者的吸烟率。     

Microalbuminuria is a poor predictor for progression of diabetic kidney disease in young type 1 diabetic patients

Conclusions: Current understanding of the prognostic and diagnostic significance of microalbuminuria is unclear.