Predictor Of Diabetic Complications Research Articles

Advanced Glycation Endproducts: A Marker of Long-term Exposure to Glycemia.

This article examines the importance of advanced glycation endproducts (AGEs) and summarizes the structure of AGEs, pathological changes associated with AGEs, the contribution of AGEs to metabolic memory, and the value of AGEs as a predictor of diabetic complications and cardiovascular disease in people with and without diabetes. As a practical focus, skin autofluorescence (SAF) is examined as an attractive approach for estimating AGE burden. The measurement of AGEs may be of significant value to specific individuals and groups, including Black and Hispanic/Latino Americans, as they appear to have higher concentrations of hemoglobin A1c (HbA1c) than would be predicted by other metrics of mean glycemia. We hypothesize that if the amount of glycation of HbA1c is greater than expected from measured glucose levels, and if AGEs are accumulating, then this accumulation of AGEs might account for the increased rate of complications of diabetes in populations with high rates of vascular disease and other complications. Thus, identifying and modifying the burden of AGEs based on measurement of AGEs by SAF may turn out to be a worthwhile metric to determine individuals who are at high risk for the complications of diabetes as well as others without diabetes at risk of vascular disease. We conclude that available evidence supports SAF as both a clinical measurement and as a means of evaluating interventions aimed at reducing the risks of vascular disease and diabetic complications.

Investigating the Significance of Glycosylated Hemoglobin A1C (HbA1C) Test in the Diagnosis and Management of Diabetic Individuals.

Background: Since the 1980s, Glycosylated hemoglobin (HbA1c) has been used as the "gold standard" for glycemic control and as a predictor of diabetes complications. HbA1c has become a solid biomarker for diagnosis and prediction of diabetes, because of the meaningful information offered by a single HbA1c test. It is also helpful in the treatment of pre-diabetes and other kinds of diabetes. Objective: To reveal sensitivity of HbA1c in contrast to other diabetes diagnostic tests, to report the performance, effectiveness and validity of HbA1c test in the diagnosing and monitoring diabetes. To find out the awareness rate of significance of HbA1c test in diabetic monitoring. Material & Methodology: A cross-sectional research was conducted through a random sample approach, during the months of September and December of 2021. A sample size of 40 patients and health professionals including technologist and Doctor were taken. The data was gathered through a pre-validated research questionnaire among patients and health workers in major hospitals of Islamabad and Rawalpindi. Data was analyzed through Statistical Package for the Social Science(SPSS) software version 22. Result: The results found that 85% patients are agree with the significance of HbA1c test in diabetic monitoring while 15% patients are disagreeing with the significance of HbA1c test in diabetic monitoring. The results also reveal that 47% health professional feel that HbA1c test has better diagnostic accuracy than other diabetes diagnostic tests, 22% believe it is more dependable than other glucose tests, and 30% believe it is successful in diabetes mellitus prognosis. Conclusion: It was determined that in assessing and managing diabetes mellitus HbA1c test is considered one of the significant diagnostic test. It has the capacity to recall the previous three months' cumulative history of Glycosylated hemoglobin. The accuracy, sensitivity and reliability of HbA1c test is very high and clear in contrast to other blood glucose diagnostic tests. HbA1c test is more accurate than both a fasting glucose test and random glucose test. Moreover, HbA1c test does not need any fasting it perform any time.

The hemoglobin glycation index predicts the risk of adverse cardiovascular events in coronary heart disease patients with type 2 diabetes mellitus.

Previous studies have shown that the hemoglobin glycation index (HGI) can be used as a predictor of diabetic complications. However, limited information is currently available to indicate the correlation between HGI and comorbidity of coronary heart disease (CHD) and diabetes. This study aimed to evaluate the potential of HGI to predict major adverse cardiovascular events (MACEs) in CHD patients with type 2 diabetes mellitus (T2DM) undergoing percutaneous coronary intervention (PCI). A total of 918 CHD patients with T2DM were enrolled in a 3-year retrospective cohort study, from December 2017 to December 2020 at the First Affiliated Hospital of Zhengzhou University. Data including fasting blood glucose (FPG/FBG) and glycated hemoglobin A1c (HbA1c) were collected. HGI was calculated as actual measured HbA1c minus predicted HbA1c. Three groups were further divided based on the levels of HGI, including low, medium, and high levels. Kaplan Meier analysis indicated that elevated HGI was strongly associated with the occurence of MACE (log-rank P < 0.001). Multivariate Cox regression analysis revealed that elevated HGI was an independent risk factor for incident MACE in CHD patients with T2DM [adjusted hazard ratio (HR): 1.473; 95% confidence interval (CI): 1.365-1.589, P < 0.001]. Hemoglobin glycation index is an independent predictor of MACE events in CHD patients with T2DM. High HGI indicates a higher risk of MACE occurrence.

Effect of Hemoglobin A1c Trajectories on Future Outcomes in a 10-Year Cohort With Type 2 Diabetes Mellitus.

BackgroundHemoglobin A1c (HbA1c) variability may be a predictor of diabetic complications, but the predictive values of HbA1c trajectories remain unclear. We aimed to classify long-term HbA1c trajectories and to explore their effects on future clinical outcomes in a 10-year cohort with type 2 diabetes mellitus (T2DM).MethodsA total of 2,161 participants with T2DM from the Beijing Community Diabetes Study were included. The 10-year follow-up was divided into two stages for the present data analysis. Stage I (from 2008 to 2014) was used to identify the HbA1c trajectories and to calculate the adjusted SD of HbA1c (HbA1c-adjSD), or the coefficient of variation of HbA1c (HbA1c-CV). Stage II (from 2014 to 2018) was used to collect the records of the new occurrence of diabetes-related clinical outcomes. Latent growth mixture models were used to identify HbA1c trajectories. Cox proportional hazards models were used to explore the relationship between HbA1c trajectories, HbA1c-adjSD, or HbA1c-CV and the future outcomes.ResultsThree HbA1c trajectories were identified, including low stable (88.34%), gradual decreasing (5.83%), and pre-stable and post-increase (5.83%). Either the risk of death or the chronic complications were significantly higher in the latter two groups compared to the low stable group after adjustment for average HbA1c and other traditional risk factors, the adjusted hazard ratios (HRs) for renal events, composite endpoint, and all-cause death for the pre-stable and post-increase group were 2.83 [95%CI: 1.25–6.41, p = 0.013], 1.85 (95%CI: 1.10–3.10, p = 0.020), and 3.01 (95%CI: 1.13–8.07, p = 0.028), respectively, and the adjusted HR for renal events for the gradual decreasing group was 2.37 (95%CI: 1.08–5.21, p = 0.032). In addition, both univariate and multivariate Cox HR models indicated that participants in the fourth and third quartiles of HbA1c-CV or HbA1c-adjSD were at higher risk of renal events compared to participants in the first quartile.ConclusionsHbA1c trajectories, HbA1c-CV, and HbA1c-adjSD could all predict diabetes-related clinical outcomes. HbA1c trajectories could reflect long-term blood glucose fluctuation more intuitively, and non-stable HbA1c trajectories may predict increased risk of renal events, all-cause death, and composite endpoint events, independent of average HbA1c.

Effect of Pharmacist-Led Intervention on Progression of Diabetic Complications at Two Tertiary Care Hospitals of Malaysia.

Background and Objective:Diabetes mellitus is a chronic disease which can lead to different complications in patients if not treated properly. An appropriate intervention from health care providers is needed to stop and decrease the progression of diabetic complication in diabetic patients. This study aimed to measure the effect of pharmacist intervention on improvement in sign and symptoms and progression of diabetic complications in diabetic patients.Methodology:Diabetic patients were randomly selected and divided into two groups from two tertiary care hospitals. Control group contained those 200 patients who were receiving usual treatment from hospitals. In contrast, the intervention group included those 200 patients who were receiving conventional treatment from hospitals together with separate counselling sessions with pharmacists from Diabetes Medication Therapy Adherence Clinic departments. The study continued for 1 year and two follow-up visits for both groups. A prevalidated data collection form was used to measure the improvement in sign and symptoms and progression of diabetic complication in diabetic patients. Statistical Package for the Social Sciences (SPSS) version 24 was used to analyze the data.Results:The average hemoglobin A1c (HbA1c) values decreased up to 1.43% in the control group and 2.82% in the intervention group. The intervention group showed significant improvement in HbA1c between groups (P < 0.05). The results of univariate and multivariate regression analysis showed that a statistically significant (P < 0.001) improvement was observed in all the predictors of diabetic complications among in the intervention group when compared with the control group.Conclusion:Statistically significant reduction in the sign and symptoms of diabetic complications was observed in the intervention group at the end of 1 year. The progression of diabetic neuropathy was significantly reduced in the pharmacist intervention group.

English

The aim of this study was to determine the correlation between glycated hemoglobin and blood sugar levels in diabetic subjects carried out in Abidjan. This cross-sectional study included 100 patients with diabetes monitored, for three months, for whom glycated blood glucose and hemoglobin were performed, this after informed consent of the patients. Pearson and Spearman correlation tests were used, at the 5% threshold. The patients with normal HbA1C and normal blood glucose accounted for 55.34 and 32%, respectively. A sedentary lifestyle and body mass index > 25 kg/m² were associated with a significant increase in the risk of increased blood glucose and HbA1C. The presence of a complication was associated with a 3.06-fold higher risk of high glycated hemoglobin (p= 0.0073), while blood glucose was not significantly associated with the onset of complications. Glycated hemoglobin was significantly correlated with blood glucose with a correlation coefficient of 0.4412 (p 0.0001). In multivariate analysis, hyperglycemia was significantly associated with alcohol consumption and non-compliance with antidiabetic treatment. Poor compliance was significantly associated with increased glycated hemoglobin (>7%) and tobacco consumption. The glycated hemoglobin was highly correlated with blood sugar, and was found to be a better predictor of diabetes complications than glycemia. Key words: Diabetes mellitus, glycated hemoglobin, blood sugar, Abidjan, Cote d’Ivoire.

880-P: Is Time-in-Range Independent of A1C? A Study in Asian Indian Population

Time-in-Range (TIR) has been recently established as a treatment target in diabetes to complement the time-tested A1c. Studies in the Caucasian population have shown that every 10% increase in TIR corresponds to 0.8% reduction in A1c. To study the relationship between TIR with A1c in the Asian-Indian population, CGM data from EMR of patients with type 1 and type 2 diabetes (n=424) followed up by a telemedicine program (DTMS) at our comprehensive diabetes care center in Kerala was obtained. Mann Whitney U test, t-test, ANOVA, and Pearson correlation coefficient were used for univariate analysis. Baseline characteristics were age 54 + 14 years, Gender frequency: F/M 127/297, diabetes duration 10.83+8.24 years, A1c 7.44+1.17 (%), eA1c 6.74+1.24 (%), and Average Blood Glucose (ABG) 146.96 + 35.62 (mg/dL). All the patients were eligible for a reduction of A1C &amp;lt;7.5%. In this subset of Asian-Indian population, our statistical analysis revealed that a TIR of &amp;gt;70% corresponds to an A1c level of &amp;lt;7.5% in agreement with the previous studies. In our telemedicine-based chronic care model, an A1c of &amp;lt;7.5% was achieved in 67.5% of the subjects. However only 36% achieved a TIR &amp;gt;70% and 66% achieved a TIR &amp;gt;60%; a finding which underscores the significance of TIR independent of A1c levels. The study suggests that TIR should evolve as a powerful target and predictor of diabetes complications and should be a routine measure in diabetes care. Disclosure J. Kesavadev: Speaker’s Bureau; Self; Biocon, Novo Nordisk Inc., Sanofi-Aventis. A. Shankar: None. G. Krishnan: None. B.D. Saboo: None. G. Sanal: None. M. Krishna B: None. S. Ts: None. S. Jothydev: None.

Serum Magnesium Level Change in Type 2 Diabetic Patients with Cardiovascular Complications

AbstractBackground: Diabetic macrovascular complications remain the main cause of morbidity and mortality in type 2 diabetes patients. Magnesium is a necessary cofactor for several enzymes that play an important role in glucose metabolism.Aim of Study: This work was designed to investigate the relation between serum magnesium and diabetic cardiovascular complications.Patients and Methods: In the present study, 120 patients with type 2 diabetes mellitus were enrolled from Internal Medicine Diabetes and Endocrine Unit Out-patient Clinic, Tanta University Hospitals, Egypt, and 30 individuals as a control within a period of one year. The enrolled individuals were divided into two groups. Group I included 30 healthy non diabetic individuals as control group. Group II included 120 type 2 diabetes patients classified into subgroups;A-30 type 2 diabetic patients without any vascular com-plications.B-30 type 2 diabetic patients with ischemic heart disease.C-30 type 2 diabetic patients with nephropathy.D-30 type 2 diabetic patients with retinopathy.Serum magnesium and other investigations were taken to evaluate the relation between serum magnesium and diabetic macrovascular complications.Result: Serum magnesium level was significantly low in patients with ischemic heart disease 1.28±0.36mg/dl. It was found using recipient characteristic observer curve for mag-nesium as a predictor of diabetic complications that serum magnesium level of 0.9mg/dl was accompanied with 76.4% sensitivity and 72% specificity for prediction of complications. While, HbA1C 7.5% was accompanied with 86.1% sensitivity and 46.2% specificity for prediction of macrovascular com-pilations. Serum magnesium level could be a predictor of occurrence of diabetic complications, but its role in pathogen-esis cannot be well stated as our data did not confirm that hypomagnesaemia is an independent risk factor for diabetes complications.Conclusion: From this study, it can be concluded that that serum magnesium level could be a predictor of occurrence of diabetic complications, but its role in pathogenesis cannot be well stated as our data did not confirm that hypomagnesaemia is an independent risk factor for diabetes complications.

The haemoglobin glycation index as predictor of diabetes-related complications in the AleCardio trial.

The haemoglobin glycation index (HGI) quantifies the interindividual variation in the propensity for glycation and is a predictor of diabetes complications and adverse effects of intensive glucose lowering. We investigated the relevance of HGI as independent predictor of complications by using data of the AleCardio trial. The AleCardio trial randomized 7226 type 2 diabetes patients with an acute coronary syndrome to aleglitazar or placebo. From 6458 patients with baseline glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG), a linear regression equation, HbA1c (%) = 5.45 + 0.0158 * FPG (mg/dl), was used to calculate predicted HbA1c and derive HGI (= observed - predicted HbA1c). With multivariate Cox regression we examined the association with major adverse cardiac events, cardiovascular mortality, total mortality and hypoglycaemia, irrespective of treatment allocation, using HGI subgroups (low, intermediate and high) and HGI as continuous variable. Patients with high HGI were younger, more often non-Caucasian, had a longer duration of diabetes, showed more retinopathy and used insulin more often. Hypoglycaemia occurred less often in the low HGI subgroup, but this difference disappeared after adjustment for duration of diabetes, insulin and sulphonylurea use. Low HGI patients were at lower risk for cardiovascular mortality (hazard ratio 0.64; 95% confidence interval 0.44-0.93, p = 0.020) and total mortality (hazard ratio 0.69; 95% confidence interval 0.50-0.95, p = 0.025), as compared with high HGI patients. Every percentage increase in HGI was associated with a 16% increase in the risk for cardiovascular mortality ( p = 0.005). The association between HGI and mortality disappeared with additional adjustment for HbA1c. HGI predicts mortality in diabetes patients with acute coronary syndromes, but no better than HbA1c.

Determining the Prevalence of Retinopathy and Its Related Factors among Patients with Type 2 Diabetes in Kerman, Iran

ObjectivesTo determine the prevalence of retinopathy and its associated factors in diabetic patients referred to a diabetes center in an Iranian city. MethodsThis was a cross-sectional, descriptive–analytical study in which a researcher-made checklist was used to collect the data of patients with type 2 diabetes in 2015. The statistical population consisted of 11,770 health records of diabetic patients registered in a second-level diabetes center. Of the 11,770 health records, 206 records with the most complete data about patients with type 2 diabetes were selected through census method. Chi-square test and logistic regression through SPSS were used for data analysis. ResultsIn this study, 93/206 diabetic patients (45.1%) had retinopathy. Female sex, age over 60, lower education level, being housewife, family history of having diabetes, longer years of having the disease, and higher level of hemoglobin A1c (HbA1c) were associated with higher risk of retinopathy. However, the association was statistically significant only for the HbA1c level (p ≥ 0.05). ConclusionAccording to this study, HbA1c level is a predictor of diabetes complications. Therefore, it is necessary for health authorities to improve diabetes management through different strategies to prevent complications to control blood sugar effectively.

Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study.

Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports using single baseline glycosyated haemoglobin (HbA1c ). Using the time-weighted mean of serial HbA1c measurements has been found to be a better predictor of diabetic complications as it reflects the glycaemic burden for that individual over time. We therefore sought to confirm this in a large cohort of patients with T2DM and incident CHF. A time-weighted mean HbA1c was calculated using all HbA1c measurements following CHF diagnosis. Patients were grouped into five categories of HbA1c (≤6.0%, 6.1-7.0%, 7.1-8.0%, 8.1-9.0%, and >9.0%). The relationship between time-weighted mean HbA1c and all-cause death after CHF diagnosis was assessed. A total of 1447 patients with T2DM met the study criteria. During a median follow-up of 2.8 years, there were 826 (57.1%) deaths, with a crude death rate of 155 deaths per 1000 person-years [95% confidence interval (CI) 144-166]. A Cox regression model, adjusted for all significant predictors, with the middle HbA1c category (7.1-8.0%) as the reference, showed a U-shaped relationship between HbA1c and outcome [HbA1c <6.0%, hazard ratio (HR) 2.5, 95% CI 1.8-3.4; HbA1c 6.1-7.0%, HR 1.4, 95% 1.1-1.7; HbA1c 8.1-9.0%, HR 1.3, 95% CI 1.0-1.6; and HbA1c >9.0%, HR 1.8, 95% CI 1.4-2.3]. Further analysis revealed a protective effect of insulin sensitizers (i.e. metformin) (HR 0.7, 95% CI 0.61-0.93) but not other drug classes. In patients with T2DM and CHF, our study shows a U-shaped relationship between HbA1c and mortality, with the lowest risk in patients with modest glycaemic control (HbA1c 7.1-8.0%) and those treated with insulin sensitizers.

Study of Adiponectin Level in Diabetic Adolescent Girls in Relation to Glycemic Control and Complication of Diabetes.

AIM:To study the relation between adiponectin level with glycemic control and complication of diabetes.PATIENTS AND METHODS:The study included 40 female adolescent type 1 diabetic patients and 40 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile and adiponectine. Urine sample was taken for assessment of albumin/creatinine ratio.RESULTS:Diabetic patients had a significantly higher diastolic blood pressure, triglyceride, total cholesterol, LDL and adiponectin than controls. Patients with diabetes complication had a significant lower BMI and HDL. On the other hand, they had higher disease duration, total cholesterol, HbA1, albumin/creatinine ratio and adiponectin. Patients with microalbuminuria had a lower BMI, higher disease duration, diastolic blood pressure and adiponectin. Patients with diabetic retinopathy had higher disease duration, insulin dose, HbA1, microalbuminuria and adiponectin. Adiponectin in diabetic patients had a significant negative correlation with BMI and positive correlation with systolic blood pressure and microlabuminuria.CONCLUSION:Serum adiponectin level is high in adolescent type 1 diabetic girls. It can be used as a predictor of diabetes complications rather than a sensitive biochemical marker for glycemic control.

Clinical utility of serum beta-2-microglobulin as a predictor of diabetic complications in patients with type 2 diabetes without renal impairment

AimAs serum beta-2-microglobulin (B2M) levels are usually elevated in patients with renal failure, they have been suggested as a surrogate marker of cardiovascular mortality for patients with chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of diabetic complications in patients with diabetes. Our objective was to evaluate the relationship between B2M and diabetic complications in patients with type 2 diabetes (T2D) and normal kidney function. MethodsA total of 366 patients with T2D and preserved renal function with no clinical evidence of cardiovascular disease were enrolled consecutively into this study. High B2M was defined as a median serum B2M level ≥ 1.8mg/L. Subclinical atherosclerosis was defined as a carotid artery intima–media thickness (C-IMT) ≥ 0.9mm or the presence of carotid plaque. The definition of diabetic nephropathy was based on the presence of albuminuria (≥ 30mg/g creatinine). ResultsPatients with high B2M were older, and had diabetes of longer duration, higher serum creatinine, microalbuminuria, and increased vascular stiffness and C-IMT compared with patients with low B2M. B2M levels were positively correlated with C-IMT and vascular stiffness, and these associations remained constant after adjusting for age. In addition, after adjusting for age, gender, body mass index, serum creatinine, hypertension, smoking and alcohol consumption, the adjusted odds ratio (OR) for atherosclerosis was 2.01 [95% confidence interval (CI): 1.02–3.94] per 1mg/L increase in B2M. The prevalences of diabetic retinopathy and nephropathy were significantly higher with a high B2M than with a low B2M. The multiple adjusted OR for diabetic nephropathy was 2.29 (95% CI: 1.11–4.72) per 1mg/L increase of B2M. ConclusionHigher serum B2M was an independent risk factor for subclinical atherosclerosis and diabetic nephropathy in patients with T2D without renal impairment.

DNA damage and cytotoxicity in adult subjects with prediabetes

Prediabetes (intermediate hyperglycemia) is a high-risk state for diabetes that is defined by higher than normal glycemic levels that are below the level required for a diagnosis of diabetes. Prediabetes is characterized by oxidative stress, yet the associated DNA damage and cytotoxicity remain unknown to date. Therefore, we evaluated the relationship between glycemic alterations, DNA damage and cytotoxicity in the lymphocytes of individuals with pre-diabetes. Fasting plasma glucose (FPG) and glycated hemoglobin (A1C) levels were quantified and used as inclusion criteria. Anthropometric parameters were also evaluated. The cytokinesis-block micronucleus cytome assay (CBMN Cyt) was used to evaluate DNA damage and cytotoxicity. FPG correlated with A1C (r=0.562, p=0.002). Because A1C is the best predictor of diabetes complications, the association between A1C and the evaluated variables was assessed. The waist–hip ratio correlated with A1C (p<0.01). Regarding DNA damage, the frequency of nucleoplasmic bridges correlated with A1C (p<0.05). Both apoptosis and necrosis correlated with A1C (p<0.05). The overall frequency of DNA damage and cytotoxicity also correlated with A1C (p<0.01). Additional studies evaluating cell cycle and cell death patterns in prediabetes are necessary.

Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature

The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. A total of 18 studies -8 on type 1 DM and 10 on type 2 DM patients-meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base.

A rat model of glycaemic variability

-independent predictorof diabetic vascular complications [1]. This conclusion isderived essentially from retrospective epidemiological ana-lyses with hard (microvascular) endpoints [2] and fromobservational and interventional studies with surrogateendpoints (oxidative stress and endothelial function, assessedwith flow-mediated dilation) [3,4]. Clearly, the correlationfound between glycaemic variability and microvascularcomplications/oxidative stress does not necessarily indicateacause–effect relationship; furthermore, the effect ofglycaemic instability on macrovascular disease is not known.As a consequence, whether glycaemic variability is causallylinked to diabetic complications and, in particular, to macro-vascular dysfunction, remains an open question.In their elegant paper, Horvath et al. [5] investigatedboth the effect of glucose fluctuation on endothelialfunction (a surrogate marker of macrovascular complica-tions) and the possible mechanisms linking glucose‘swings’ to vascular damage. In particular, they comparedthe effect of glycaemic variability on endothelial dysfunc-tion in four rat models: poor glycaemic control (PGC),good glycaemic control, untreated diabetic (UD) and non-diabetic. Interestingly, although the ‘global glycaemicexposition’, mathematically expressed by the AUC of their48 h glycaemic profiles and correlated with 48 h meanglucose level [6], was significantly higher in UD rats thanin PGC rats, endothelial dysfunction was greater in thePGC rats. This finding supported their conclusion that ‘theoscillation of blood glucose level itself is a more importantcontributor to the loss of endothelial function in diabetesthan the average level of mean blood glucose level per se’.In our opinion, this conclusion is not completely supportedby the data presented. In fact, the different variability of theglycaemic profiles of PGC versus UD rats is onlypresumptive and is not supported by an objective math-ematical analysis, i.e. comparison of one or more indices ofvariability (mean amplitude of glycaemic excursions[MAGE], standard deviation, continuous overall net gly-caemic action [CONGAn] and others) [6] between the twogroups. If the indices of variability for PGC and UD ratswere similar, then this would indicate that the betterendothelial function of UD rats might be related to anunexplored variable. Therefore, the conclusion should stateonly that mean blood glucose is not enough to completelyexplain vascular dysfunction.

The True Value of HbA1c as a Predictor of Diabetic Complications: Simulations of HbA1c Variables

AimThe updated mean HbA1c has been used in risk estimates of diabetic complications, but it does not take into account the temporal relationship between HbA1c and diabetic complications. We studied whether the updated mean HbA1c underestimated the risk of diabetic complications.MethodContinuous HbA1c curves for 10,000 hypothetical diabetes patients were simulated over an average of 7 years. Simulations were based on HbA1c values encountered in clinical practice. We assumed that each short time interval of the continuous HbA1c curves had a long-lasting effect on diabetic complications, as evidenced by earlier studies. We tested several different HbA1c variables including various profiles, e.g. different duration, of such a long-lasting effect. The predictive power of these variables was compared with that of the updated mean HbA1c.ResultsThe predictive power of the constructed HbA1c variables differed considerably compared to that of the updated mean HbA1c. The risk increase per standard deviation could be almost 100% higher for a constructed predictor than the updated mean HbA1c.ConclusionsThe importance of good glycemic control in preventing diabetic complications could have been underestimated in earlier hallmark studies by not taking the time-dependent effect of HbA1c into account.

Assessing Glycemia in Diabetes Using Self-monitoring Blood Glucose and Hemoglobin A1c

With the increasing prevalence of diabetes, successful management of blood glucose control is increasingly important. Current approaches to assessing glycemia include the use of self-monitoring of blood glucose (SMBG) and hemoglobin A1c (HbA1c). To assess the evidence underlying the use of these 2 modalities, to evaluate confounders and sources of error in each test, to describe upcoming developments, and to reach evidence-based conclusions on their optimal use. Reports identified from MEDLINE searches (1976-2005) using relevant terms were selected for quality and relevance to the stated questions. Particular attention was paid to larger cohort studies, clinical trials, meta-analyses, and established recommendations. If used properly SMBG gives an acceptably accurate reflection of immediate plasma glucose levels. Study results vary, but in general, the evidence supports a positive effect of regular SMBG for improving glycemia, particularly in individuals treated with insulin. The best timing of SMBG and its frequency are controversial issues, but the clinical recommendation is for regular monitoring with frequency depending on the treatment and the instability of glycemia. In the relatively near term, SMBG could gradually be replaced by continuous glucose monitoring. HbA1c measures long-term glycemic control, reflecting a time-weighted mean over the previous 3 to 4 months. There are a number of physiologic and methodologic confounders that can affect HbA1c, but standardization of assays has been well established. The main value of HbA1c is its use as a predictor of diabetic complications and the proven effect of improved control of HbA1c on complication risk. A reasonable target value for HbA1c is less than 7%. A new method for measuring HbA1c may cause significant changes in the recommended levels, the numbers reported, and even the name of the test. Assessing glycemia in diabetes can be a challenge, but approaches are available that promote successful management of blood glucose and may thereby lead to a significant reduction in morbidity and mortality related to diabetes.

Predictors of glycemic control in children with Type 1 diabetes: The importance of race

Diabetes is a common cause of kidney failure and blindness among young adults, particularly of African-American descent. Since glycemic control is a predictor of diabetes complications, we evaluated the impact of multiple factors including a special multidisciplinary management program on glycosylated hemoglobin in children with Type 1 diabetes. Data was collected from pediatric diabetes clinics in New Orleans, LA and Baltimore, MD. In New Orleans, hemoglobin A 1c was higher in African-American patients 12.5±3.3% ( n=71) vs. 10.7±2.1% ( n=80) in Caucasian children, p<0.0001. Longer duration of diabetes was also associated with higher hemoglobin A 1c in both races. The effect of race on hemoglobin A 1c was independent of the influence of sex, insurance status, body mass index (BMI) z-score, and number of clinic visits. Covariate analysis with mean blood glucose levels indicated that higher hemoglobin A 1c was attributable to higher mean blood glucose levels in African-American children. From the Baltimore data, a multidisciplinary intervention program led to improved total glycosylated hemoglobin for Caucasian patients but not for African-American children. Poorer glycemic control of African-American children is likely to predispose them to a higher likelihood of developing microvascular complications as they mature. Standard hospital-based multidisciplinary programming for diabetes management may have limited effectiveness in improving glycemic control of African-American children with diabetes. Innovative intervention programs are needed for these high-risk patients.

Longitudinal patterns of glycemic control and diabetes care from diagnosis in a population-based cohort with type 1 diabetes. The Wisconsin Diabetes Registry.

Glycosylated hemoglobin is an indicator of long-term glycemic control and a strong predictor of diabetic complications. This paper provides a comprehensive description of glycemic control (total glycosylated hemoglobin (GHb)) up to 4.5 years duration of diabetes by age, duration, and sex in a population-based cohort (n = 507) aged less than 20 years followed from diagnosis of Type 1 diabetes in Wisconsin during 1987-1994 Important aspects of demographics and diabetes care are described to allow comparison with other populations. Since large variations between laboratories are known to exist in the measurement of GHb, levels are also interpreted relative to the frequency of short-term complications. GHb increased after diagnosis, but leveled off after 2-3 years. Peak GHb values occurred in the age group 12-15 years. The within-individual standard deviation in GHb between tests, adjusted for age and duration was 1.6%. The mean GHb at last testing was 11.3%, with a standard deviation across individuals of 2.9%. The majority (74%) of individuals saw a diabetes specialist at least once. The mean number of insulin injections per day increased from 2.2 to 2.5 across the 4.5-year duration, and the insulin dose increased from 0.6 to 0.9 units per day per kg body weight. Despite the quite satisfactory level of care, 38% of subjects had GHb levels associated with significant short-term complications.