Can interstitial glucose assessment replace blood glucose measurements?

Current treatment regiments for individuals depending on exogenous insulin are based on measurements of blood glucose obtained through painful finger sticks. The shift to minimal or noninvasive continuous glucose monitoring primarily involves a shift from blood glucose measurements to devices measuring subcutaneous interstitial fluid (ISF) glucose. As the development of these devices progresses, details of the dynamic relationship between blood glucose and interstitial glucose dynamics need to be firmly established. This is a challenging task insofar as direct measures of ISF glucose are not readily available. The current article investigated the dynamic relationship between plasma and ISF glucose using a model-based approach. A two-compartment model system previously validated on data obtained with the MiniMed Continuous Glucose Monitoring System (CGMS) is reviewed and predictions from the original two-compartment model were confirmed using new data analysis of glucose dynamics in plasma and hindlimb lymph (lymph is derived from ISF) in the anesthetized dog. From these data sets, the time delay between plasma and ISF glucose in dogs was established (5-12 minutes) and a simulation study was performed to estimate the errors introduced if ISF is taken as a surrogate for blood. From the simulation study, the error component resulting from the differences in plasma and ISF glucose was estimated to be < 6% during normal day-to-day use in an individual with diabetes (error component calculated as the standard deviation of the ISF/plasma glucose differences under conditions where the maximal time delay was used). This difference is most likely within the variance between arterial and venous blood glucose. We conclude that the differences between plasma and ISF glucose will not be a significant obstacle in advancing the use of ISF as an alternative to blood glucose measurements.     

Continuous glucose monitoring in patients with type 2 diabetes: Why? When? Whom?

The overall assessment of glycaemic control in patients with type 2 diabetes should normally include the monitoring of three parameters that are usually depicted as the 'glucose triad': HbA(1c), fasting plasma glucose (FPG) and postprandial glucose (PPG) excursions. However one additional marker, the so-called 'glucose variability' might be as important as the three others since it has been demonstrated that both upward and downward glucose fluctuations are potent activators of oxidative stress. Even though many methods have been proposed for assessing glucose fluctuations, the 'mean amplitude glucose excursions' (MAGE) index remains the 'gold standard'. However MAGE estimation requires the use of continuous glucose sensors. Despite the debate on the reliability and cost of the devices that permit glucose monitoring, we suggest that interventional trials designed to evaluate the effects of glucose fluctuations on diabetic complications should benefit from the use of continuous glucose monitoring systems (CGMSs). More prosaically, the use of these technologies could be extended to current clinical care of type 2 diabetic patients especially for motivating them to accept earlier insulin treatments in case of 'oral antidiabetic drug secondary failure', and further for choosing the most appropriate insulin regimen.     

Self‐monitoring of blood glucose in type‐2 diabetes: what is the evidence?

BACKGROUND: There is a controversy about self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes who are not using insulin. Randomized trials are limited in duration, size, and validity. METHODS: Systematic search for randomized trials and observational studies published since 1990. For inclusion studies had to report on SMBG in type 2 diabetes managed with oral hypoglycaemic agents and/or diet alone, HbA(1c) or clinical outcome, have at least 50 patients and be of at least 6 months' duration. RESULTS: Three randomized trials with 1000 patients were included, though all had interventions differing in the amount of education on SMBG, and in the population studied. The two larger studies had statistically significantly lower HbA(1c) levels with SMBG. Thirteen observational studies had information on over 60,000 patients. Smaller studies had lower initial HbA(1c) and showed no association between SMBG and laboratory or clinical improvement. Larger studies tended to have higher initial HbA(1c) and did show an association between SMBG and laboratory or clinical improvement. Overall, improvement in glycaemic control with SMBG tended to be seen in studies with initial HbA(1c) above 8%. CONCLUSIONS: It is likely that SMBG is beneficial in some circumstances, for example as an educational tool, for patients with type 2 diabetes not using insulin who have poor glycaemic control. More information is needed at the level of the individual patient, rather than group means, and about timing and frequency of monitoring, response to those results, what constitutes effective patient education, and long-term clinical outcomes.     

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.     

Gestational ‘impaired glucose tolerance’: should the cut-off be raised to 9 mmol l−1?

It has been suggested that the diagnostic criterion for the 2-h value of the 75 g oral glucose tolerance test in pregnancy be raised to 9 mmol 1⁻¹. In order to determine whether patients with a 2-h value of between 8 and 8.9 mmol 1⁻¹ should be classified as normal, we performed a retrospective study on patients with gestational diabetes mellitus treated with diet only who delivered within 1 year, and categorized them into three groups according to the 2-h value as follows: group A (8–8.9 mmol 1⁻¹), group B (9–10.9 mmol l⁻¹), and group C (≥11.0 mmol 1⁻¹). These groups were compared with a control group with normal oral glucose tolerance test results and who delivered within the same 1-year period. Group A patients were significantly different from the control group in maternal age, parity, fasting value in the oral glucose tolerance test, maternal body mass index, gestational age at delivery, incidence of large for dates infants, and placental weight, but were similar to group B for most of these parameters. Group C was significantly different from both the control group and group A for most of the above parameters. Our results suggest that the current World Health Organization criterion for the diagnosis of gestational diabetes mellitus should be maintained. © 1998 John Wiley & Sons, Ltd.     

Nocturnal hypoglycaemias in type 1 diabetic patients: what can we learn with continuous glucose monitoring?

AimIn type 1 diabetic patients (T1DM), nocturnal hypoglycaemias (NH) are a serious complication of T1DM treatment; self-monitoring of blood glucose (SMBG) is recommended to detect them. However, the majority of NH remains undetected on an occasional SMBG done during the night. An alternative strategy is the Continuous glucose monitoring (CGMS), which retrospectively shows the glycaemic profile. The aims of this retrospective study were to evaluate the true incidence of NH in T1DM, the best SMBG time to predict NH, the relationship between morning hyperglycaemia and NH (Somogyi phenomenon) and the utility of CGMS to reduce NH.MethodsEighty-eight T1DM who underwent a CGMS exam were included. Indications for CGMS evaluation, hypoglycaemias and correlation with morning hyperglycaemias were recorded. The efficiency of CGMS to reduce the suspected NH was evaluated after 6–9 months.ResultsThe prevalence of NH was 67% (32% of them unsuspected). A measured hypoglycaemia at bedtime (22–24 h) had a sensitivity of 37% to detect NH (OR = 2.37, P = 0.001), while a single measure ≤ 4 mmol/l at 3-hour had a sensitivity of 43% (OR = 4.60, P < 0.001). NH were not associated with morning hyperglycaemias but with morning hypoglycaemias (OR = 3.95, P < 0.001). After 6–9 months, suspicions of NH decreased from 60 to 14% (P < 0.001).ConclusionNH were highly prevalent and often undetected. SMBG at bedtime, which detected hypoglycaemia had sensitivity almost equal to that of 3-hour and should be preferred because it is easier to perform. Somogyi phenomenon was not observed. CGMS is useful to reduce the risk of NH in 75% of patients.     

The proposed terminology ‘A<Subscript>1c</Subscript>-derived average glucose’ is inherently imprecise and should not be adopted

The proposed use of a more precise standard for glycated (A(1c)) and non-glycated haemoglobin would lead to an A(1c) value, when expressed as a percentage, that is lower than that currently in use. One approach advocated to address the potential confusion that would ensue is to replace 'HbA(1c)' with a new term, 'A(1c)-derived average glucose.' We review evidence from several sources suggesting that A(1c) is, in fact, inherently imprecise as a measure of average glucose, so that the proposed terminology should not be adopted.     

Sodium–glucose cotransporter 2 inhibitors represent a paradigm shift in the prevention of heart failure in type 2 diabetes patients

Recent major clinical trials of the use of sodium–glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes have shown that they reduce three-point major adverse cardiovascular events, cardiovascular death, hospitalization for heart failure (HF) and a composite renal outcome. These beneficial effects of SGLT2 inhibitors are also evident in type 2 diabetes patients with a previous history of atherosclerotic cardiovascular disease or advanced renal disease. HF is a major determinant of the prognosis of diabetes patients. Although HF with low ejection fraction can be effectively treated with antihypertensive drugs, these treatments do not reduce mortality in HF patients with preserved ejection fraction (HFpEF). HFpEF is clinically characterized by left ventricular diastolic dysfunction, perivascular fibrosis and stiffness of cardiomyocytes, defined as “cardiomyopathy”. Therefore, HFpEF is considered to be an entirely separate entity to HF with low ejection fraction. Recent studies have suggested that HFpEF might be treatable using SGLT2 inhibitors, which ameliorate visceral adiposity, insulin resistance, hyperglycemia, hyperlipidemia, volume overload, hypertension and cardiac inflammation. In the final part of the present review, we discuss the biochemical and molecular mechanisms of the effects of SGLT2 inhibitors in type 2 diabetes patients with HFpEF. These involve amelioration of the low nitric oxide production and oxidative stress, a reduction in cardiac inflammatory cytokine signaling, inhibition of Ca²⁺ overload, and an improvement in cardiac energy metabolism as a result of ketone body production. Investigations of the beneficial effects of SGLT2 inhibitors on cardiorenal outcomes, including hospitalization for HF, are now being carried out in preclinical and clinical studies.     

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for ‘hypoglycaemia’?

Objectives Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria. Methods A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol/l, low glycaemia as 2.2–4.4 mmol/l and hyperglycaemia as >8.3 mmol/l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC). Results There was a significant difference between blood glucose levels in children who died (median 4.6 mmol/l) and survivors (median 7.6 mmol/l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64–0.88) for case fatality per 1 mmol/l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10–67.00; and 5.21, 1.86–14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13–0.91). The ROC [area under the curve at 0.753 (95% CI 0.684–0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol/l, (sensitivity 64.5% and specificity 75.1%). Conclusions If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol/l.     

Analysis of the Nova Stat Strip® glucose meter for real-time blood glucose determinations during glucose clamp studies: "don't swap horses in midstream"

Proper performance of glucose clamps is critically dependent on reliable blood glucose (BG) measurements. A number of requirements have to be fulfilled by a system that aims to replace the laboratory devices that are currently in use. Many more aspects need to be taken into account besides the accuracy of BG measurement. It might very well be that the BG meter studied by Rabiee and colleagues in this issue of Journal of Diabetes Science and Technology fulfills most or all of such requirements; however, these aspects have to be tested more thoroughly before one switches from an established measurement method to the Nova Stat Strip® glucometer.     

Does reviewing fasting plasma glucose results patterns before glycosylated hemoglobin testing in type-2 diabetic patients lead to better testing decision?

AimsGlycosylated hemoglobin (HbA_1c) test for blood glucose control in type-2 diabetic patients is recommended at least once annually under the guidelines of the Thai National Health Security Office (NHSO) benefits coverage. With limited resources and capability for HbA_1c testing in most primary-care providers, this study explored patterns of fasting plasma glucose (FPG) tests for proper timing of HbA_1c test would increase value of the money spent.MethodsA retrospective review of laboratory findings of 4906 type-2 diabetic outpatients in two university hospitals in Thailand was conducted. Percentages of discordant results between the indexed FPG and HbA_1c tests were compared between the patient groups with different FPG patterns before HbA_1c testing and the control group of randomly selected cases.ResultsHaving HbA_1c tested after two and three consecutively normal FPG tests (OO and OOO patterns) were found to have significantly less discordance than the control group (−9.6% and −15.7%). HbA_1c testing after two abnormal and one normal consecutive FPG tests (XXO pattern) gained the discordant results by 24.8%.ConclusionsSome FPG patterns were more predictive of HbA_1c findings than focusing on one-time FPG results. Reviewing and recognizing certain patterns of FPGs prior to taking HbA_1c tests can lead to better HbA_1c testing decision than randomly prescribing the tests.     

Can dietary fructans lower serum glucose?

Background: Convincing evidence indicates that the consumption of inulin‐type fructans, inulin, and oligofructose has beneficial effects on blood glucose changes in animal models, although data in humans have been considered equivocal. As such, a systematic review of available literature on humans was conducted to evaluate the effectiveness of dietary inulin‐type fructans on serum glucose. Methods: Thirteen eligible randomized controlled trials (RCT), published from 1984 to 2009, were identified using a comprehensive search strategy involving the PubMed, Medline, and Cochrane Library databases. Exclusion criteria, such as the absence of a control group, lack of information on the quantity of inulin‐type fructans used, and lack of glucose values at outcome, were established. Results: Upon review, only four of the 13 trials (31%) showed a decrease in serum glucose concentration and only one of these was statistically significant. The remaining nine trials showed no significant changes in serum glucose concentration. Conclusion: Based on the present systematic review, it does not appear that inulin‐type fructans have a significant lowering effect on serum glucose in humans. More RCT are needed to determine whether inulin‐type fructans, inulin, and oligofructose have beneficial effects on blood glucose in humans.