Importance of glucagon in the control of futile cycling as studied in alloxan-diabetic dogs

Summary In order to determine the role of glucagon in futile or substrate cycling in diabetes, we measured tracer determined glucose kinetics during a combined infusion of 2-³H-glucose (total glucose production) and 6-³H-glucose (glucose production) in six alloxan-diabetic dogs. The animals received either a 420 min infusion of (1) somatostatin alone (0.3 g·kg^–1· min^–1), (2) somatostatin with insulin replacement (100 U·kg^–1min^–1) or (3) glucagon (6 ng·kg^–1· min^–1) together with somatostatin and transient insulin replacement. When somatostatin was given alone, plasma glucagon (p<0.004) and insulin (p<0.0001) were suppressed. Glucose production and disappearance and plasma glucose concentrations fell (p<0.0001), but the metabolic clearance of glucose did not change significantly. In the basal state, futile cycling comprised 29±4%, 33±4% and 33±3% of total glucose production in the three goups of studies, which is high compared to normal dogs. The absolute rate of futile cycling fell slightly but significantly from 10.0±1.7 to 8.3±1.7 mol·kg·^–1min^–1 (p<0.0008). When insulin replacement was given during somatostatin infusion to correct for the small somatostatin-induced insulin suppression, there were similar changes in plasma glucagon, glucose concentrations and glucose kinetics as seen during the infusion of somatostatin alone. Futile cycling decreased to a slightly greater extent from 12.8±2.8 to 9.5±1.7mol·kg^–1·min.^–1 (p<0.02). When glucagon was infused together with somatostatin and insulin replacement, plasma glucagon (p<0.0002) increased and plasma glucose levels rose (p<0.001) due to a transient increase in glucose production. Metabolic clearance of glucose did not change significantly. There was a marked increase in futile cycling from 12.2±1.7 to 21.7±1.7mol· kg^–1·min^–1 (p<0.0001) in response to exogenous glucagon excess. There was a slight (p<0.01) drop in free fatty acid levels with somatostatin. Free fatty acid levels nearly doubled (p<0.025) with the infusion of glucagon together with somatostatin. In conclusion, (a) futile cycling was increased in alloxan-diabetic dogs; (b) glucagon suppression can suppress futile cycling only if total insulin deficiency is prevented; and (3) hyperglucagonaemia increases futile cycling, and this effect is more pronounced during insulin deficiency.     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

糖调节受损的危害与干预

糖调节受损是糖尿病重要的前期阶段,可能发展为糖尿病并形成大血管病变,也可能逆转为正常葡萄糖状态.因此,积极的干预治疗是十分重要的.生活方式的干预与药物治疗可以延缓或避免糖尿病的发生,而且生活方式的改变比药物更为有效.     

No-Coding Strategies for Glucose Monitors: ��No Coding�� of Glucose Test Strips: A Roche Perspective

Introduction

Glucose test strips vary slightly from batch to batch. These variations are accounted for by a batch-specific “code”: a set of parameters defining the relationship between the signal change induced on the glucose test strip and the blood glucose concentration.

Methods

We assessed the impact on accuracy of miscoding the ACCU-CHEK^® Aviva system across a wide range of glucose test strip batches and glucose levels, throughout the shelf life of the glucose test strips.

Results

The deviations in coding that we investigated had no effect on clinical action. Additionally, we showed, with mathematical modeling of a worst-case scenario, that the probability of an error altering clinical action is low. The batch-specific code of glucose test strips ensures the accuracy and safety of each blood glucose measurement. In addition to the parameters directly related to the blood glucose measurement, the electronic code chip contains the expiration date of the test strips and can deliver firmware updates for upgrades to the glucose meter.

Conclusions

We eliminated the handling step of coding and retained all the advantages of coding. In Roche''s newest all-in-one glucose meter, the ACCU-CHEK Compact Plus system, the batch-specific code is integrated into the drum that contains the glucose test strips. As a result, changing the drum containing the glucose test strips automatically changes the glucose test strip code. Patients with diabetes who use the ACCU-CHEK Compact Plus glucose meter do not have to be concerned with coding.     

中老年糖尿病流行病学调查方法探讨

对９１７例４０岁以上健康人利用６种方法同时进行糖尿病（ＤＭ）流行病学调查。按ＷＨＯ标准初筛出ＤＭ９４例，糖耐量异常（ＩＧＴ）９２例。方法①ＦＰＧ≥７．８ｍｍｏｌ／Ｌ；②ＦＰＧ≥６．７ｍｍｏｌ／Ｌ；③餐后２ｈ血糖≥１１．１ｍｍｏｌ／Ｌ；④空腹尿糖≥＋；⑤餐后２ｈ尿糖≥；⑥餐后２ｈ尿糖≥和（或）ＦＰＧ≥６．７ｍｍｏｌ／Ｌ并联阳性。结果①④法特异度高，灵敏度低，只查出ＤＭ１／３许。②⑤法灵敏度也低。③法灵敏度９８．１％，特异性１００％，但大规模健康普查时就要抽两次静脉血，难以做到。⑥法灵敏度８０．４％，特异性９４．０％，仅次于③法，操作与普查同步，可作为健康普查时早期诊断Ⅱ型ＤＭ初筛；即对普查时血尿化验不够ＤＭ标准而餐后２ｈ尿糖≥或ＦＰＧ≥６．７ｍｍｏｌ／Ｌ的可疑患者再进行餐后２ｈ血糖或ＯＧＴＴ确诊ＤＭ或ＩＧＴ，为大规模防治ＤＭ打下基础。     

血糖及其他体液葡萄糖测定进展

本文从糖尿病医患角度介绍血糖测定的进展。主要从血浆糖测定到毛细血管全血糖测定，以及近年的微创组织液糖测定及无创糖测定。较详细地讨论了毛细血管全血糖测定的特点和误差的原因。     

Impaired fasting glucose and impaired glucose tolerance in urban population in India.

AIMS: To study prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in urban Indians and their demographic and anthropometric characteristics. METHODS: Data on capillary blood glucose (OGTT), anthropometric and demography details were available in 10 025 subjects (M : F 4711 : 5314) aged > or = 20 years. Glucose tolerance was categorized as normal, isolated IFG, isolated IGT, IFG + IGT and diabetes using the fasting and 2-h blood glucose (2hBG; 75-g glucose load) values. Subjects with known diabetes were excluded. RESULTS: Age-standardized prevalences of IFG, IGT and newly detected diabetes were 8.7%, 8.1% and 13.9%, respectively. IFG was more prevalent in women (9.8%) than in men (7.4%) (chi2 = 13.62, P = 0.0002), while the gender differences in IGT (men 8.4%, women 7.9%) and diabetes (men 13.3%, women 14.3%) were not significant. Body mass index and waist circumference were higher in glucose-intolerant groups than in normal glucose tolerance (NGT). Prevalence of diabetes, IGT and IFG + IGT increased with age. Among the IFG, 4% had diabetes and 27.1% had IGT using 2hBG criteria. In IFG, the fasting and 2hBG values were not correlated. CONCLUSIONS: Prevalences of IFG and IGT were similar in urban Indians and an overlap occurred in only less than half of these subjects. IFG was more common in women. Subjects with IFG were older and had more adverse anthropometric characteristics in comparison with NGT. IFG did not show an increasing trend with age.     

Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals

Background

This study investigated continuous glucose profiles in nondiabetic subjects.

Methods

Continuous interstitial glucose measurement was performed under everyday life conditions (2 days) and after ingestion of four meals with standardized carbohydrate content (50 grams), but with different types of carbohydrates and variable protein and fat content. Twenty-four healthy volunteers (12 female, 12 male, age 27.1 ± 3.6 years) participated in the study. Each subject wore two microdialysis devices (SCGM1, Roche Diagnostics) simultaneously.

Results

The mean 24-hour interstitial glucose concentration under everyday life conditions was 89.3 ± 6.2 mg/dl (mean ± SD, n = 21), and mean interstitial glucose concentrations at daytime and during the night were 93.0 ± 7.0 and 81.8 ± 6.3 mg/dl, respectively. The highest postprandial glucose concentrations were observed after breakfast: 132.3 ± 16.7 mg/dl (range 101–168 mg/dl); peak concentrations after lunch and dinner were 118.2 ± 13.4 and 123.0 ± 16.9 mg/dl, respectively. Mean time to peak glucose concentration was between 46 and 50 minutes. After ingestion of standardized meals with fast absorption characteristics, peak interstitial glucose concentrations were 133.2 ± 14.4 and 137.2 ± 21.1 mg/dl, respectively. Meals with a higher fiber, protein, and fat content induced a smaller increase and a slower decrease of postprandial glucose concentrations with peak values of 99.2 ± 10.5 and 122.1 ± 20.4 mg/dl, respectively.

Conclusions

This study provided continuous glucose profiles in nondiabetic subjects and demonstrated that differences in meal composition are reflected in postprandial interstitial glucose concentrations. Regarding the increasing application of continuous glucose monitoring in diabetic patients, these data suggest that detailed information about the ingested meals is important for adequate interpretation of postprandial glucose profiles.     

Accuracy and reliability of the Nova StatStrip® glucose meter for real-time blood glucose determinations during glucose clamp studies

Aims/Hypothesis

The Andres clamp technique, which requires accurate and timely determination of glucose, utilizes the Beckman or Yellow Springs Instruments (YSI) glucose analyzers. Both instruments require maintenance, a dedicated operator, preparation of a plasma sample, and a duplicate measurement that takes ≥2 minutes. The Nova StatStrip glucose meter was evaluated for accuracy, reliability, and near-real-time availability of glucose.

Methods

Blood samples from 24 patients who underwent 6-hour clamp studies and 12 patients who had a standardized meal tolerance test (SMT) were measured. Specimens were analyzed simultaneously and immediately upon collection by Beckman, YSI, and Nova.

Results

Of 1004 data pairs for the Nova device versus Beckman, the Nova data points ranged from 32 to 444, while Beckman ranged from 42 to 412. The coefficient for the slope of Beckman versus Nova was 1.009 (r = 0.978). Using error grid analysis, the number and percentage of values for Nova were 976 (97.2%) in the A zone and 28 (2.8%) in the B zone. Of 399 data pairs for the Nova device versus YSI, the Nova data points ranged from 46 to 255, whereas YSI ranged from 47 to 231. The coefficient for the slope of YSI versus Nova was 1.023 (r = 0.989). All Nova readings fell in the A zone. Time required for final reading, in duplicate, was 15 seconds for Nova and 120–180 seconds for Beckman and YSI.

Conclusions

The simplicity of Nova and its reliability, accuracy, and speed make it an acceptable replacement device for Beckman and YSI in the conduct of clamps, especially when perturbations require rapid glucose determination.     

Methodology for Quantifying Fasting Glucose Homeostasis in Type 2 Diabetes: Observed Variability and Lability

Background:

Increased glycemic variability is associated with an increase risk of adverse clinical outcomes in diabetes. Central to the understanding of diabetes is glucose homeostasis. “Good” homeostasis is equated to low glycemic variability, and “poor” homeostasis is linked to greater glycemic variability. We have, therefore, developed a method with the aim to objectively quantify the domain of glucose–insulin homeostasis. We have termed this method as Observed Variability And Lability (OVAL).

Method:

Blood samples for the measurement of glucose and insulin concentrations were acquired every 2 min for 120 min from 12 patients with type 2 diabetes mellitus [T2DM; median (range) age 35 (25–47) years and duration of diabetes 7 (2–9) years receiving oral hypoglycemic treatment] and 27 controls [aged 38(30–53) years] with an equal split of genders and equal distribution of body mass indexes. The insulin–glucose time variant data form the boundaries of OVAL, defined as the ellipse enclosing the 95% confidence intervals of the insulin and glucose concentrations plotted on an x−y scatter graph and normalized to ensure equal weighting of insulin and glucose.

Results:

Less precise OVAL homeostasis was observed in subjects with T2DM, by a factor of 4, in comparison with controls [OVAL, T2DM 7.8(3.8) versus controls 1.9(1.0); p =.0003]. The assessment remained statistically robust (p <.001) with increased sampling intervals up to 8 min.

Conclusion:

The OVAL model is a robust method for measuring glucose–insulin homeostasis in controls and T2DM subjects (available online at http://www.oval-calc.co.uk). Deranged glucose–insulin homeostasis is the hallmark of diabetes and OVAL has the capacity to quantify in the fasting state.     

Alarms for Continuous Glucose Monitors: Methods of Evaluating the Utility of Continuous Glucose Monitor Alerts

Background

The evaluation of continuous glucose monitor (CGM) alert performance should reflect patient use in real time. By evaluating alerts as real-time events, their ability to both detect and predict low and high blood glucose (BG) events can be examined.

Method

True alerts (TA) were defined as a CGM alert occurring within ± 30 minutes from the beginning of a low or a high BG event. The TA time to detection was calculated as [time of CGM alert] – [beginning of event]. False alerts (FA) were defined as a BG event outside of the alert zone within ± 30 minutes from a CGM alert. Analysis was performed comparing DexCom™ SEVEN^® PLUS CGM data to BG measured with a laboratory analyzer.

Results

Of 49 low glucose events (BG ≤70 mg/dl), with the CGM alert set to 90 mg/dl, the TA rate was 91.8%. For 50% of TAs, the CGM alert preceded the event by at least 21 minutes. The FA rate was 25.0%. Similar results were found for high alerts.

Conclusion

Continuous glucose monitor alerts are capable of both detecting and predicting low and high BG events. The setting of alerts entails a trade-off between predictive ability and FA rate. Realistic analysis of this trade-off will guide patients in the effective utilization of CGM.     

Accuracy performance of the Medtronic NexSensor™ for 6 days in an inpatient setting using abdomen and buttocks insertion sites

Background

Users of continuous glucose monitoring are concerned with product accuracy and choice of insertion site. The Medtronic NexSensor™ was evaluated for accuracy during 6 days of wear when inserted in the abdomen and buttocks areas.

Methods

Adults (ages 18–75) with type 1 diabetes wore two sensors simultaneously for 6 days, one each inserted in the abdomen and buttocks. Subjects underwent a frequent blood sampling study for 12 hours, during which time reference blood glucose values were obtained every 15 minutes and compared to sensor values.

Results

Sixty-three subjects were enrolled, and 61 subjects completed the study. The mean agreement rate between sensor and blood glucose values was 75.5% [95% confidence interval (CI), 69.5, 81.4] at the abdomen site, 73.8% (95% CI, 68.8, 78.8) at the buttocks site, and 75.6% (95% CI, 70.8, 80.4) when sensor and reference data were combined between sites. Over 90% of paired sensor-reference values on Clarke error grids were within the A and B ranges. The mean absolute relative differences were 17.1% at the abdomen site, 16.5% at the buttocks site, and 16.8% when sites were combined.

Conclusion

The NexSensor was accurate for inpatient, frequent-sample testing for 6 days when inserted into the abdomen and buttocks. The results of this study also provide evidence that both the abdomen and buttocks are suitable as sensor insertion sites.     

Laboratory Advances in Hemoglobin A1c Measurement: The Correlation of Hemoglobin A1c to Blood Glucose

The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of “average blood glucose” as though “blood glucose” were itself a simple idea. When we consider all the blood glucose forms—arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting—we can start to see that this is not a simple issue.Nevertheless, it seems as though HbA1c correlates to any single glucose measurement. Having more than one measurement and taking those measurements in the preceding month improves the correlation further. In particular, by having glucose measurements that reflect both the relatively lower overnight glucose levels and measurements that reflect the postprandial peaks improves not only our ability to manage diabetes patients, but also our understanding of how HbA1c levels are determined. Modern continuous glucose monitoring (CGM) devices may take thousands of glucose results over a week. Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c.The ability to relate HbA1c to average glucose may become a popular method for reporting HbA1c, eliminating current concerns regarding differences in HbA1c standardization. Hemoglobin A1c expressed as an average glucose may be more understandable to patients and improve not only their understanding, but also their ability to improve their diabetes management.     

Clinical implications of combined glucose intolerance in treatment-naïve hypertensive patients

ABSTRACT

Background: This study is the first study to evaluate clinical significance of combined glucose intolerance (CGI) in treatment-naïve hypertensive patients. Methods: We compared the results of demographic, anthropometric, clinical, laboratory examinations, echocardiography, arterial stiffness, central blood pressure (BP) and ambulatory BP monitoring (ABPM) between the groups according to fasting blood sugar (FBS), postprandial 2 hour blood glucose (PP2) and gender in treatment-naïve hypertensive patients. A total of 376 concecutively-eligible patients were categorized as follows: (1) normal glucose tolerance (NGT); FBS<100 mg/dL and PP2 < 140 (2) isolated glucose intolerance (IGI); 100≤FBS<126 or 140≤PP2 < 200, but not both 100≤FBS<126 and 140≤PP2 < 200 (3) CGI; both 100≤FBS<126 and 140≤PP2 < 200. Results: Males were divided into NGT (n = 58, 33.1%), IGI (n = 88, 50.3%), CGI (n = 29, 16.6%) and females were divided into NGT (n = 59, 43.1%), IGI (n = 48, 35%), CGI (n = 30, 21.9%). In males multivariate analyses revealed that mitral average E/Ea (IGI vs CGI, p = 0.022), brachial-ankle pulse wave velocity baPWV(Rt.) (IGI vs CGI, p = 0.026), baPWV(Lt.) (IGI vs CGI, p = 0.018), office systolic BP (SBP) (NGT vs. CGI, p = 0.005; IGI vs. CGI, p = 0.001), office diastolic BP (DBP) (NGT vs. CGI, p = 0.034; IGI vs. CGI, p = 0.019), night-time SBP (NGT vs. CGI, p = 0.049; IGI vs. CGI, p = 0.018) were significantly higher in the CGI group than in the NGT or IGI group. However, there were no significant differences between the female groups. Conclusions: Treatment-naïve hypertensive males with CGI revealed subclinical diastolic dysfunction, arterial stiffness, and BPs.     

Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM

Summary Carbohydrate ingestion results in a fall in glucagon concentration in non-diabetic but not in diabetic individuals. To determine if, and the mechanism by which, lack of postprandial suppression of glucagon contributes to hyperglycaemia, nine subjects with insulin-dependent diabetes mellitus (IDDM) ingested 50 g of glucose containing both [2-³H] glucose and [6-³H] glucose on two occasions. [6-¹⁴C] glucose, insulin and low-dose somatostatin were infused intravenously at the same rates on both occasions. A basal glucagon infusion was started either at the same time (constant glucagon) or 2 h following (suppressed glucagon) glucose ingestion. This resulted in lower (p<0.001) glucagon concentrations during the first 2 h of the suppressed than during the constant glucagon study days (63±1 vs 108±2 pg/ ml). Lack of suppression of glucagon led to higher (p<0.01) postprandial glucose concentrations (10.3±0.9 vs 8.1±0.7 mmol/l) and a greater (p<0.02) integrated glycaemic response. The excessive rise in glucose was due to higher (p<0.02) rates of postprandial hepatic glucose release during the constant than during the suppressed glucagon study days, whether measured using either [6-³H] glucose (2.6±0.2 vs 2.0±0.2 mmol·kg^–1 per 6 h) or [2-³H] glucose (3.0±0.3 vs 2.4±0.2 mmol·kg^–1 per 6 h) as the meal tracer. Glucose disappearance, initial splanchnic glucose clearance and hepatic glucose cycling did not differ on the two occasions. Thus, the present studies demonstrate that lack of postprandial suppression of glucagon, by increasing hepatic glucose release, contributes to hyperglycaemia in subjects with IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus     

Postchallenge glucose rises with increasing age even when glucose tolerance is normal.

AIMS: Ageing increases the likelihood of developing diabetes, with associated cardiovascular disease. In a cross-sectional study, we sought to determine whether age is associated with an increase in glucose concentrations 1 h after an oral glucose challenge (1-h OGTT), even when glucose tolerance is normal (NGT). METHODS: Among subjects in the NHANES II database, 2591 subjects with NGT and documented 1-h OGTT glucose concentrations were studied. The relationship between age and 1-h OGTT glucose concentrations was assessed in a multivariable linear regression analysis. RESULTS: In a multivariable linear regression analysis, each 10-year increase in age conferred an additional 0.20 mmol/l increase in the 1-h OGTT glucose (P < 0.0001). Moreover, an interaction between age and gender was found such that 1-h OGTT glucose concentrations rose more rapidly with increasing age in men than in women. The impact of age on 1-h OGTT glucose was independent of both fasting and 2-h OGTT glucose concentrations. CONCLUSIONS: One-hour OGTT glucose concentrations rise significantly with age even in subjects with NGT. Further investigation is warranted to explore the pathophysiological significance of such age-related impairment of glucose handling, which might increase the risk of cardiovascular disease even when patients do not meet criteria for the diagnosis of diabetes or prediabetes.     

Investigations on glucose uptake in isolated human leucocytes from normal and diabetic subjects

Summary 1. Leucocyte preparations have been obtained from the blood of 135 healthy control persons and 10 poorly-controlled insulin-dependent diabetics according to a procedure described earlier. Cells were suspended in a Krebs-Ringer-Bicarbonate-Buffer. Glucose uptake, lactate production and cell glucose space were determined after incubating the cells for 1 h at 37° C in an atmosphere of O₂/CO₂ (95/5). Extracellular water-space of the cell sediment was corrected by measuring U-¹⁴C-sucrose levels in the medium before and after addition to the cell sediment. — 2. The cells showed intact structures and amoeboid motility under the light-microscope as well as under the phase-contrast-microscope. During an incubation lasting 1 h, the ATP/ADP quotient diminished by about 20%; the following metabolites: glucose-6-phosphate, fructose-1,6-diphosphate, 1,3-phosphoglycerate, pyruvate and lactate increased slightly up to markedly, especially glucose-6-phosphate and lactate. — 3. Sources of methodological errors were investigated in preliminary experiments. Disregarding corrections for the extracellular space of the cell sediments led to a dilution effect which imitates an apparent glucose uptake. For measurements of intracellular glucose and cell glucose space the procedure of Crofford and Renold provided the best results. Falsely high values for cell glucose have been found using the glucose oxidase reaction. — 4. Glucose uptake of healthy leucocytes increases at first steeply, later on less with rising medium glucose concentrations. Addition of insulin (50–500 mU/ml) gave no consistent effects. At medium glucose concentrations of 400 and 600 mg/100 ml intracellular glucose could be demonstrated with statistical significance. Intracellular glucose and cell glucose space were not affected by insulin to any marked degree. Determinations of lactate production indicated that human leucocytes utilize the largest portion of glucose via glycolysis. — 5. At medium glucose concentrations of 600 mg/100 ml leucocytes from diabetics who had received no insulin for 14 h prior to incubation showed a significant diminution of glucose uptake. — 6. Theoretical curves for inward transport and phosphorylation have been calculated from the data for glucose uptake and intracellular glucose concentration.The authors are greatly indepted to Prof. Wilbrandt, Department of Pharmacology, University Bern, for advice and discussion.     

A simple way to estimate mean plasma glucose and to identify Type 2 diabetic subjects with poor glycaemic control when a standardized HbA1c assay is .

AIMS: To evaluate the relationship between HbA(1c) and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels, and to estimate the mean plasma glucose (mPG) derived from FPG and PPG that would predict Type 2 diabetic subjects with poor glycaemic control. METHODS: FPG, PPG and HbA(1c) values from 565 Type 2 diabetic patients (247 men and 318 women) were recorded. Linear regression analysis and Pearson's correlation was used to determine the relationship between HbA(1c), FPG and PPG. FPG and PPG were included as explanatory variables of HbA(1c) in linear regression analysis. RESULTS: The American Diabetes Association's objective of achieving an HbA(1c) level < 7.0% was obtained in 26.2% of the patients. The coefficients of FPG and PPG which determined HbA(1c) were similar. Therefore, mPG was calculated using the equation (FPG + PPG)/2. Pearson's correlation coefficient for HbA(1c) and FPG, PPG and mPG were 0.723 (P < 0.0001), 0.734 and 0.761 (P < 0.0001), respectively. A mPG cut-off value of 10 mmol/l predicted an HbA(1c) > 7% in the whole population, with a sensitivity of 84.2% and specificity of 80.4%. The area was high (0.90) in receiver-operating characteristic (ROC) curve analysis performed to examine the performance of mPG to predict HbA(1c) > 7%. CONCLUSIONS: The mPG derived from FPG and PPG correlates strongly with HbA(1c). We therefore suggest that using a cut-off of 10 mmol/l for mPG may be appropriate in diabetes management in the primary-care setting, where most management of Type 2 diabetes occurs.