J Roth

HbA1c and Age in Non-Diabetic Subjects: An Ignored Association?

Objective: Target HbA1c values given in the most National Therapeutic Guidelines for patients with diabetes and cut-off HbA1c values for diabetes diagnosis are usually not taking the age of the respective patients into account; despite the fact that an increase in HbA1c in subjects without diabetes with age is known for some time. In order to further quantify the association between age and HbA1c in non-diabetic subjects an analysis of one German register was performed. Methods: In this cross-sectional study we analyzed data from 7 699 visits of 2 921 patients without diabetes (age 46.6 y [range 18-93 y]; 69.1% women; BMI 27.6±6.4 kg/m²) who had at least one HbA1c and blood glucose measurement. Data were drawn from an electronic patient record system (EMIL™) in which data were collected between 01/1992 and 01/2014. The patients were divided in 6 age groups (< 30 years [n=1 057];>30-40 years [n=1 160];>40-50 years [n=1 693];>50-60 years [n=1 523];>60-70 years [n=1 310];>70 years [n=956]) and the HbA1c values of these groups were compared. Patients with: gestational diabetes, use of systemic glucocorticoids, malignant neoplasm, age<18 y at time of first visit and IGT were excluded. HbA1c measurements were DCCT adjusted. Results: Patients with age>70 years have a 0.47% [5.14 mmol/mol] higher HbA1c compared to those<30 years. The mean HbA1c of the age groups was:<30 4.98% [30.96 mmol/mol],>30-40 5.07% [31.99 mmol/mol],>40-50 5.17% [33.10 mmol/mol],>50-60 5.33% [34.79 mmol/mol],>60-70 5.42% [35.79 mmol/mol] and>70 years 5.45% [36.10 mmol/mol]. In a multiple linear model the regression coefficient for each year of age increase was β=0.0074 (p<0.001); thus age results in an increase of 0.074% in HbA1c per decade. Conclusion: HbA1c increases significantly with ageing in people without diabetes. The use of different cut-off values for every age range for diagnosis of diabetes should be discussed.

Comparison of HbA1c Measurements using 3 Methods in 75 Patients Referred to One Outpatient Department

OBJECTIVE HbA1c is the most important surrogate parameter to assess the quality of diabetes care and is also used for the diagnosis of diabetes mellitus (DM) since 2010. We investigated the comparability of 3 HbA1c methods in the city of Jena (Germany). METHODS The HbA1c determination was carried out in 50 healthy subjects and 24 people with DM (age 51.2±16.3 years, HbA1c 6.8±2.2%) with 3 different hemoglobin A1c testing methods at 4 locations in one city. Our laboratory (HPLC method) served as a reference for comparing the results. All methods are IFCC standardized and all devices are certified by the interlaboratory test. RESULTS The mean HbA1c of people without diabetes was: laboratory A (TOSOH G8, HPLC) 5.7±0.3%; laboratory B (TOSOH G8, HPLC) 5.5±0.3%, laboratory C (VARIANT II) 5.2±0.3%; laboratory D (COBAS INT.) 5.6±0.3%. All differences are significant (p=0.001).The mean HbA1c of patients with mild to moderate elevated HbA1c was: Laboratory A 7.5±0.9%; B 7.3±1.0%; C 7.0±0.9%; D 7.5±1.1%. Differences are significant (p=0.001) except between laboratory A and D (p=0.8).The mean HbA1c of patients with massively increased HbA1c was: laboratory A 11.5±1.8%; laboratory B 11.4±1.8%; laboratory C 10.8±1.6%; laboratory D 11.5±1.5%. Differences between laboratory A and C, as well as between C and D were significant (p=0.001). CONCLUSION The mean IFCC standardized HbA1c from 75 people differs by up to 0.5% absolute between 4 laboratories. This difference is clinically significant and may lead to misdiagnosis and wrong treatment decisions, while HbA1c value from one patient were analyzed in different laboratories within a short time.

Higher HbA1c Measurement Quality Standards are Needed for Follow-Up and Diagnosis: Experience and Analyses from Germany.

Measurement of HbA1c is an essential laboratory measure for the follow-up and therapy decision-making in patients with diabetes. HbA1c is one of the measurands in laboratory medicine that have to be successfully checked according to the criteria of the guidelines of the German Medical Association (Rili-BAEK) in external quality assurance using the reference method value concept, when applied in patient care. The allowed deviation of ±18% in external quality assessment (EQA) and ± 10% in internal quality control has been ultimately met by virtually all the different manufacturers and methods. However, such broad limits for permissible deviations are not suitable in view of medical requirements in patient care. The low-level acceptance criteria also depends on the previously used EQA materials used in Germany. In fact, HbA1c measurement results that are imprecisely measured or come from incorrectly calibrated devices are difficult to identify. With implementation of unprocessed fresh EDTA blood, the situation has changed. Until now systems with unit use reagents for point-of-care testing (POCT) of HbA1c are not mandatory to participate in EQA schemes in Germany. This paper outlines why there was a need to narrow the acceptance limits listed within the Rili-BAEK for HbA1cs internal (to ± 3%) and external (to ± 8%) quality controls in EQA schemes for Germany, which will take place after a transition period in the next years. Higher quality in HbA1c measurements will help to avoid misdiagnosis of diabetes as well as potential over- or undertreatment of patients at risk for diabetes.

People with Type 2 Diabetes on Premixed Insulin Therapy: How is the Daily Insulin Dose Partitioned and are there Effects on the Metabolic Control?

AIM To investigate the correctness of the recommendation for dose distribution in premixed insulin therapy, with two thirds of daily insulin dose before breakfast and one third of daily insulin dose before dinner. METHODS The individual insulin dose distribution and metabolic control of people with Type 2 diabetes treated with premixed insulin therapy were studied in a cross sectional study involving 199 patients in a university outpatient department and 2 general practices in 2010. RESULTS All 199 patients were treated with premixed human insulin. The mean pre-breakfast dose was 57% (min. 32%, max. 83%) and the mean pre-dinner dose 43% (17-67%) of the total daily insulin. A pre-breakfast dose of exactly two thirds of total daily insulin was used by 6.5% (n=13), about two thirds, i. e., 60-70%, was injected by 27.6% of the patients. The diurnal insulin distribution<60%, 60% up to 70% and > 70% pre-breakfast insulin did not make any difference in HbA1c, which was 7.3% (56 mmol/mol) each. CONCLUSION The quite common recommendation in German and Austrian medical textbooks, that premixed insulin therapy should consists of a dose distribution with two thirds before breakfast and one third before dinner, is not observed in daily practice. Diurnal insulin dose distribution and HbA1c are not associated in this cohort. Novelty statement: The circadian insulin dose distribution of 2/3 before breakfast and 1/3 before dinner could not be confirmed for patients with diabetes type 2 and conventional insulin therapy. No correlation between metabolic control and insulin circadian insulin dose distribution was detected.