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Concept: Glycated hemoglobin


OBJECTIVE We tested the hypothesis of an independent cross-sectional association between obstructive sleep apnea (OSA) severity and glycated hemoglobin (HbA(1c)) in adults without known diabetes. RESEARCH DESIGN AND METHODS HbA(1c) was measured in whole-blood samples from 2,139 patients undergoing nocturnal recording for suspected OSA. Participants with self-reported diabetes, use of diabetes medication, or HbA(1c) value ≥6.5% were excluded from this study. Our final sample size comprised 1,599 patients. RESULTS A dose-response relationship was observed between apnea-hypopnea index (AHI) and the percentage of patients with HbA(1c) >6.0%, ranging from 10.8% for AHI <5 to 34.2% for AHI ≥50. After adjustment for age, sex, smoking habits, BMI, waist circumference, cardiovascular morbidity, daytime sleepiness, depression, insomnia, sleep duration, and study site, odds ratios (95% CIs) for HbA(1c) >6.0% were 1 (reference), 1.40 (0.84-2.32), 1.80 (1.19-2.72), 2.02 (1.31-3.14), and 2.96 (1.58-5.54) for AHI values <5, 5 to <15, 15 to <30, 30 to <50, and ≥50, respectively. Increasing hypoxemia during sleep was also independently associated with the odds of HbA(1c) >6.0%. CONCLUSIONS Among adults without known diabetes, increasing OSA severity is independently associated with impaired glucose metabolism, as assessed by higher HbA(1c) values, which may expose them to higher risks of diabetes and cardiovascular disease.

Concepts: Diabetes mellitus, Blood sugar, Sleep, Sleep apnea, Obstructive sleep apnea, Glycated hemoglobin, Hypopnea, Medical conditions related to obesity


HbA1c ≥ 6.5% has been recommended as a diagnostic criterion for the detection of diabetes mellitus (DM) since 2010 because of its convenience, stability and significant correlation with diabetic complications. Nevertheless, the accuracy of HbA1c compared to glucose-based diagnostic criteria varies among subjects of different ethnicity and risk profile.

Concepts: Nutrition, Insulin, Diabetes mellitus, Diabetes, Blood sugar, Glucose tolerance test, Insulin resistance, Glycated hemoglobin


The One Drop | Mobile app supports manual and passive (via HealthKit and One Drop’s glucose meter) tracking of self-care and glycated hemoglobin A1c (HbA1c).

Concepts: Diabetes mellitus, Diabetes, Glycated hemoglobin, Glycation, Anthony Cerami


What is the extent and effect of excessive testing for glycated hemoglobin (HbA1c) among adults with controlled type 2 diabetes?

Concepts: Diabetes mellitus, Diabetes, Glycated hemoglobin, Glycation


Background The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. Methods In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. Results Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. Conclusions Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 numbers, NCT01961622 and NCT01778348 .).

Concepts: Insulin, Diabetes mellitus, Diabetes mellitus type 1, Diabetes, Blood sugar, Hypoglycemia, Glycated hemoglobin, Glycation


Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.

Concepts: Genetics, Biology, Diabetes mellitus type 2, Diabetes mellitus, Diabetes, Glycated hemoglobin, Glycation, Anthony Cerami


Background: It was recently suggested that scaling and root planing (SRP) may help to improve glycemic and metabolic control in patients with chronic periodontitis (CP) and type 2 diabetes mellitus (DM2); however, the effectiveness of SRP in this role remains unclear. This meta-analysis assesses the effectiveness of SRP in improving glycemic and metabolic control in patients with CP and DM2. Methods: A literature search of electronic databases was performed for articles published through May 16, 2012, followed by a manual search of several dental journals. A meta-analysis was conducted according to the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Weighted mean differences (MDs) and 95% confidence intervals (CIs) were calculated for glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL and LDL, respectively). All outcomes were evaluated as changes from baseline to the end of follow-up. Heterogeneity was assessed with the χ(2)-based Cochran Q test and I(2) statistic. The level of significance was set at P <0.05. Results: After the study selection process, five randomized clinical trials were included. Results of the meta-analysis indicated that SRP was effective in the reduction of HbA1c (MD = 0.65; 95% CI 0.43 to 0.88; P <0.05) and FPG (MD = 9.04; 95% CI 2.17 to 15.9; P <0.05), but no significant differences were found in the reduction of TC, TG, HDL, or LDL. No evidence of heterogeneity was detected. Conclusion: The meta-analysis results seem to support the effectiveness of SRP in the improvement of glycemic control in patients with CP and DM2; however, future studies are needed to confirm these results.

Concepts: Cholesterol, Nutrition, Myocardial infarction, Diabetes mellitus, Evidence-based medicine, Systematic review, Diabetes, Glycated hemoglobin


Glycated hemoglobin (HbA1c) has been recently adopted as a diagnostic marker of type 2 diabetes. However, its usage is currently limited to fresh blood samples. To allow retrospective HbA1c measurement in blood banks developed in large epidemic studies, here, we contribute to validate HbA1c assessment in frozen versus fresh blood samples from a cohort of diabetic/nondiabetic adult subjects. HbA1c was measured by HPLC in 237 fresh whole blood samples and on the same samples after a 12-month storage and a further 6-month-refrozen storage. Mean HbA1c ± SD in fresh, frozen, and refrozen samples was 6.9 ± 1.2, 6.6 ± 1.1, and 6.4 ± 1.0 % for the Diabetes Control and Complications Trial and 52 ± 13, 49 ± 12, and 46 ± 11 mmol/mol for the International Federation of Clinical Chemistry and Laboratory Medicine reference, respectively. A significant correlation was found between fresh/frozen and fresh/refrozen (R = 0.994 and 0.993, P < 0.001) samples. HbA1c relative error ratio (%RER) between frozen/refrozen and fresh samples significantly correlated with HbA1c and depended on fresh value range, increasing in the five HbA1c classes (<6.0, 6.0-6.5, 6.5-7, 7-8, ≥8 %, corresponding to <42, 42-48, 48-53, 53-64, ≥64 mmol/mol, P < 0.001). In particular, the 6.5 % (48 mmol/mol) HbA1c diagnostic cutoff of fresh samples identified two classes reflecting significant differences in %RER (2.8 ± 2.0 and 3.3 ± 1.7; P < 0.05) between frozen and fresh samples. In conclusion, our results demonstrate a high correlation between data from fresh and frozen samples, with a very limited %RER between the two measurements, which increases with baseline HbA1c levels. Accordingly, when analyzing biobank frozen specimens for diagnostic purpose, the effect of the HbA1c range should be taken into account.

Concepts: Blood, Diabetes mellitus, Measurement, Diabetes, Blood plasma, Glycated hemoglobin, Glycation, Blood donation


AIMS: Gait dysfunction in subjects with diabetes mellitus (DM) contributes to falling and subsequent injuries. Using a portable device (GaitMeter™), we measured gait parameters in DM patients with and without diabetic peripheral neuropathy (DPN) during flat surface walking. We hypothesized that DM patients with DPN and neuropathic pain (NeP) would have greater gait step variability than those with DPN without NeP. METHODS: Subjects with DPN and at least moderate NeP (DPN-P), DPN without NeP (DPN-NoP), DM without DPN, and control subjects without DM were assessed. Our outcome measure was gait variability for step length and velocity. DPN severity was quantified using the Toronto Clinical Scoring System and the Utah Early Neuropathy Score. Falls and their outcomes were retrospectively quantified. RESULTS: Each cohort contained≥20 subjects. Durations of DM and HbA1C were greatest amongst DPN cohorts. DPN-P participants had greater variability of step length and step velocity, except for DM only participants. DPN-P participants also reported greater risk of hospitalizations for fall-related injuries, and greater fear of falling. Modest negative relationships emerged for step length with step velocity, reported falls and pain severity. CONCLUSIONS: NeP contributes to gait variability, potentially contributing to the risk of falling in DM patients.

Concepts: Diabetes mellitus, Diabetes, Rheumatoid arthritis, Pain, Glycated hemoglobin, Peripheral neuropathy, Diabetic neuropathy, Gait abnormality


Since the discovery of the relation between increased concentrations of fast haemoglobin fractions in patients with diabetes mellitus compared to concentrations in subjects without diabetes mellitus by Samuel Rahbar and co-workers in 1969, glycated haemoglobin A1c (HbA1c) has become a “gold standard” for glucose management in patients with diabetes mellitus. Recently, HbA1c has been advocated as a diagnostic marker for diabetes mellitus, which further underlines the importance of HbA1c. There are currently more than 30 methods available on the market with an analytical performance ranging from poor to state of the art. This review describes the biochemistry of HbA1c and the concepts of analytical and biological variation with respect to the measurement of HbA1c. Subsequently, aspects regarding the discovery of HbA1c are described. In addition, an overview is given on the assays methods that are currently available for the measurement of HbA1c. Finally, recommendations for the minimally required analytical performance characteristics of the current HbA1c assays are presented.

Concepts: Insulin, Diabetes mellitus, Glucose, Diabetes, Blood sugar, Glycated hemoglobin, Glycation, Anthony Cerami