Point-of-Care Glucose and Lipid Profile Measures Using a Human Point-of-Care Device in Mouse Models of Type 2 Diabetes Mellitus,Aging, and Alzheimer Disease

A point-of-care (POC) device to measure mouse glucose and lipid profiles is an important unmet need for cost-effective, immediate decision making in research. We compared metabolic analyte profiles obtained using a human clinical POC device with those from a veterinary laboratory chemical analyzer (LCA). Unfasted terminal blood samples were obtained by cardiac puncture from C57Bl/6J mice used in a diet-induced obesity model of type 2 diabetes mellitus; age-matched C57Bl/6J controls; a transgenic mouse model of Alzheimer’s disease on a C57BL/6J background (16 wk old); and aged C57BL/6J mice (24 to 60 wk old). Aliquots of the blood were immediately assayed onsite using the POC device. Corresponding serum aliquots were sent analyzed by LCA. Measures from the POC and LCA devices were compared by using the Bland–Altman and Passing–Bablok methods. Of a total of 40 aliquots, LCA results were within reported reference ranges for each model. POC results that fell beyond the device range were excluded from the analyses. The coefficient of determination and Passing–Bablok analysis demonstrated that POC glucose and HDL had the best agreement with LCA. The Bland–Altman analysis found no value-dependent bias in glucose and no significant bias in HDL. The remaining lipid analytes (cholesterol and triglyceride) showed significant bias. Until an improved, validated mouse POC device with lipid profile capability is available, the POC device that we tested appears adequate for screening glucose and HDL in mouse blood. Disadvantages of this clinical POC device are the narrow human ranges relative to ranges found in mice and its limited precision as compared with the LCA. This study demonstrates that when the samples are within the device range limits, this human POC device can accurately track metabolic syndrome and be used to compare patterns in glucose and HDL.

During the last few decades, clinical point-of-care (POC) testing technology has been a fast-growing field with a variety of medical applications. The benefits of POC devices include streamlining the treatment process, reducing lab costs, and operating in low resource environments.¹³ In the domains of diagnostic testing and disorders requiring continuous monitoring, POC devices fill a gap in healthcare that provides better patient experiences and quality of care.Currently a limited number of POC devices have been designed for veterinary use,^9,16,23 and only a few of the available human clinical POC devices have been tested for accuracy when used in preclinical animal models.^10,16,22,23 The ability to conduct a POC analysis for type 2 diabetes mellitus (T2DM) and aging mice would provide several benefits to animal research, including diagnostic test convenience and immediate results. POC testing requires only a small blood volume of 5 to 40 µL, thus simplifying the blood collection process and allowing repeated and frequent sampling from each subject. Finally, use of POC devices provides a less costly alternative to the cost of a laboratory clinical analyzer (LCA) or a contract with a commercial veterinary laboratory. Within the past few years, several POC devices for human use have been modified and further developed to become self-testing devices for blood oxygen, continuous glucose monitoring, lipid profile or analytes such as lactate, creatinine, cholesterol, uric acid, hemoglobin, and illicit drugs.^4,21 However, none of these extended POC devices have been assessed for use in mice.Our laboratory studies mouse metabolic models of T2DM, aging, and Alzheimer disease (AD). To track diabetes severity and determine on the onset of a metabolic syndrome, the mice undergo frequent longitudinal glucose and lipid profile screening, which requires methodologies that require a very small blood sample for each draw.⁷ The present pilot study evaluates a recently developed human POC device that can measure glucose and a full lipid profile for its utility in mice. Groups of mice with normal and abnormal glucose and lipid profiles were used to test the full range of potential results. Our analysis compares values obtained with the POC device and with a veterinary LCA (as a ‘gold standard’).     

Comparison of near-patient capillary glucose measurement and a risk assessment questionnaire in screening for type 2 diabetes in a high-risk population in rural India

OBJECTIVE

To assess the utility of a point-of-care (POC) capillary blood glucose measurement as compared with routine clinical parameters in predicting undiagnosed diabetes in a low-resource rural India setting.

RESEARCH DESIGN AND METHODS

Nine hundred and ninety-four participants aged >30 years and stratified by age and sex were randomly selected from 20 villages in India. A clinical questionnaire, sampling for laboratory venous fasting plasma glucose (FPG), and POC capillary blood glucose assay were performed simultaneously. Diabetes diagnosis was based on the World Health Organization (WHO) definition using FPG. The capacity of the POC glucose to predict the presence of diabetes was assessed and compared with the questionnaire using area under the receiver operating characteristic curves (AUCs).

RESULTS

The AUC for POC glucose alone in predicting diabetes was 0.869 (95% CI 0.810–0.929). This was significantly better (P < 0.001 for AUC comparison) than the models based upon clinical variables alone (AUC for the best clinical model including age, BMI, hypertension, waist circumference: 0.694 [95% CI 0.621–0.766]). POC glucose appropriately reclassified the risk of up to one-third of participants ranked according to the clinical models. Adding the clinical variables to the POC glucose assay did not significantly improve the discriminatory capability beyond that achieved with the POC glucose measurement alone (all P > 0.37).

CONCLUSIONS

POC glucose testing appears to be a simple and reliable tool for identifying undiagnosed diabetes in a high-risk, resource-poor rural population. However, studies evaluating the cost effectiveness of introducing POC glucose testing are needed prior to widespread implementation.The prevalence of type 2 diabetes is rapidly increasing around the world (1). Developing countries are facing the largest increases both in absolute and relative terms (1). It is predicted that this will have devastating consequences on the economies and health systems of these countries. Successful prevention and early management of diabetes is therefore a major health priority (1,2).In many regions, up to 50% of people with diabetes remain undiagnosed (1,3,4). Failure to improve these levels of detection will mean that the opportunity to improve health outcomes with early intervention will be lost. Early treatment with successful glucose control significantly reduces the morbidity and mortality associated with diabetes (5,6). Earlier detection of diabetes also allows for the implementation of other treatments that reduce the vascular complications of diabetes (5,6).Universal screening for diabetes is not currently recommended due to a lack of good evidence for an accurate test. However, targeted screening is advocated in certain ethnic groups deemed at increased risk of diabetes (2). For some ethnic groups, implementation of targeted screening may require the entire population to be screened. This applies for instance to Asian Indian populations, which are at greater risk of developing diabetes (7) and have a high prevalence of diabetes both in urban (4) and rural settings (3). However to successfully apply screening to such populations requires accurate, safe, and low-cost diagnostic strategies that are easy to implement (8).In resource-poor settings, clinical variables–based risk assessment questionnaires or point-of-care (POC) glucose analysis may be reasonable screening tools (9). Both require little expertise and allow an individual''s risk of having undiagnosed diabetes to be immediately determined so that only those at high risk require a confirmatory diagnostic test. However, the value of risk assessment questionnaires (9–13) and POC glucose analysis (14–16) in resource-poor settings remains unclear. Additionally the performance of these different screening methods has not been compared in rural Asian Indian populations.The aim of this study was to quantify and compare the accuracy of strategies based on POC glucose, clinical variables, and the combination of both in predicting undiagnosed diabetes in an asymptomatic, resource-poor rural Asian Indian population.     

Interference of in vitro hemolysis complete blood count

Background

Hemolysis may occur in vivo, under pathological conditions, or in vitro, related to pre‐analytical errors. Hemolyzed samples may produce unreliable results, leading to errors in diagnostic and monitoring evaluations. This study aims to evaluate the interference of in vitro hemolysis on the interpretation of the parameters of the blood cell‐counting performed by the impedance method.

Methods

Peripheral blood samples were collected in anticoagulant K2‐EDTA and subsequently divided into three 1.0 mL aliquots. The first aliquot was not subjected to any intervention, and the second and third aliquots were passed 5 and 10 times through a small‐gauge needle to produce scalar amounts of hemolysis. Hematological tests were performed by Hemacounter 60‐RT 7600^®.

Results

Comparison of the samples with different degrees of hemolysis showed a decrease in red blood cells count and hematocrit counts and increase in mean corpuscular hemoglobin concentration and platelet count in samples with a high degree of hemolysis. According to the accepted clinical point of view, the samples with a high degree of hemolysis exceeded the desirable bias, presenting decrease in red blood cells count, hematocrit and mean corpuscular volume, and increase in red cell distribution width, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet counts. However, samples with a mild degree of hemolysis showed only a slight increase in mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet count.

Conclusion

This study demonstrated that in vitro hemolysis can decrease the clinical and analytical reliability of the assessment of the blood count.

     

Analysis of intraosseous blood samples using an EPOC point of care analyzer during resuscitation

Background

In the early phases of resuscitation in a critically ill patient, especially those in cardiac arrest, intravenous (IV) access can be difficult to obtain. Intraosseous (IO) access is often used in these critical situations to allow medication administration. When no IV access is available, it is difficult to obtain blood for point of care analysis, yet this information can be crucial in directing the resuscitation. We hypothesized that IO samples may be used with a point of care device to obtain useful information when seconds really do matter.

Correlation between capillary and arterial blood gas parameters in an ED

Background and aims

Sampling from arteries for the analysis of blood gases is a common procedure in emergency departments (ED). The procedure is painful for the patients and causes concern for the medical personnel due to possible complications, such as hematoma, infection, ischemia, and formation of fistula or aneurism. The present study compared the results of capillary and arterial blood gases analyses (CBG and ABG) to emphasizing a less aggressive technique with the fewest complications for this procedure.

Materials and methods

In the comparative/analytical study, the results of ABG and CBG for 187 patients referring to the ED of a teaching hospital were compared using SPSS 18 statistical software (SPSS, Chicago, IL) in relation to the mean partial pressure of oxygen (Po₂), partial pressure of carbon dioxide (Pco₂), base excess (BE), bicarbonate (HCO₃), serum acidity (pH), and saturation of hemoglobin oxygen (SaO₂).

Results

Saturation of hemoglobin oxygen, HCO₃, pH, Pco₂, Po₂, and BE exhibited significant statistical correlation between ABG and CBG (P = .001). The average correlations between capillary and arterial samples were 0.78 for pH, 0.73 for Pco₂, 0.71 for BE, 0.90 for HCO₃, 0.77 for Po₂, and 0.52 for SaO₂. Comparison of the parameters means did not exhibit significant differences between arterial and capillary samples except for Po₂ and SaO₂ (P > .05).

Conclusion

There appear to be strong correlation between samples collected from the finger tip capillaries with the arterial blood samples in relation to the analysis of blood gas.     

Is integrated nursing home care cheaper than traditional care? A cost comparison

Background

It is generally assumed that integrated care has a cost-saving potential in comparison with traditional care. However, there is little evidence on this potential with respect to integrated nursing home care.

Aims and objectives

• • 

  To portray the costs of traditional and integrated nursing home care.

• • 

  To explore the cost-saving potential of integrated care.

Design/methods/settings/participants

Between 1999 and 2003, formal and informal caregivers of different nursing homes in the Netherlands recorded activities performed for residents with somatic or psycho-social problems. In total, 23,380 lists were analysed to determine the average costs of formal and informal care per activity, per type of resident and per nursing home care type. For formal care activities, the total personnel costs per minute (in Euro) were calculated. For informal care costs, two shadow prices were used.

Results

Compared to traditional care, integrated care had lower informal direct care costs per resident and per activity and lower average costs per direct activity (for a set of activities performed by formal caregivers). The total average costs per resident per day and the costs of formal direct care per resident, however, were higher as were the costs of delivering a set of indirect activities to residents with somatic problems.

Conclusions

The general assumption that integrated care has a cost-saving potential (per resident or per individual activity) was only partially supported by our research. Our study also raised issues which should be investigated in future research on integrated nursing home care.     

Are Hemoglobin Levels Elevated in Type 1 Diabetes?

OBJECTIVE

While lower hemoglobin is generally associated with adverse events in diabetes, we have recently observed in type 1 diabetes that those with overt nephropathy had hemoglobin levels as high as 18.8 g/dl. We thus explored whether hemoglobin concentrations are generally higher in type 1 diabetes.

RESEARCH DESIGN AND METHODS

Baseline (1986–1988) hemoglobin levels from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of type 1 diabetes were compared with general population data from the National Health and Nutrition Examination Survey (NHANES) III in the same age range as the EDC population (aged 8–48 years).

RESULTS

Both male and female EDC study participants had significantly higher hemoglobin levels than their NHANES III counterparts (men: 16.0 vs. 15.1 g/dl, P < 0.0001; women: 14.1 vs. 13.3 g/dl, P < 0.0001). The difference between the two populations was greatest in adolescent female subjects.

CONCLUSIONS

Hemoglobin levels may be higher in type 1 diabetes than in the general population, which may have important clinical implications.Although low hemoglobin is generally associated with adverse events in diabetes (1) and kidney disease (2), we have recently observed relatively high hemoglobin levels (as high as 18.8 g/dl) among individuals with type 1 diabetes and overt nephropathy (3) compared with the general renal disease population (4). This led us to question whether hemoglobin levels are generally elevated in type 1 diabetes. We therefore assessed 652 individuals from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of type 1 diabetes and compared the hemoglobin levels observed with those of the general National Health and Nutrition Examination Survey (NHANES) III population.     

Comparison of the diagnostic characteristics of two B-type natriuretic peptide point-of-care devices

Background

B-type natriuretic peptide (BNP) is used to diagnose heart failure (HF).

Objective

To compare the accuracy of two commercially available point-of-care (POC) devices for measuring B-type natriuretic peptide (BNP) in emergency department (ED) patients with suspected heart failure using the central laboratory testing results as the criterion standard.

Methods

Venous blood samples were collected from adults with suspected heart failure and split into three samples for BNP analysis: central laboratory (Siemens ADIVA Centaur; Siemens, Deerfield, IL), Triage BNP POC device (Biosite, San Diego, CA), and i-STAT BNP POC device (Abbott, East Windsor, NJ). The criterion standard for BNP levels was the central laboratory.

Results

Two hundred fifty patients were enrolled. Mean (SD) age was 70.7 (13.8) years; 200 (80%) were over age 55 years; 146 (58.4%) were male. A final hospital discharge diagnosis of heart failure was made in 108 (42%) patients. The i-STAT system yielded a result within a median of 9 min (interquartile range [IQR] 9–10 min). The Triage device yielded a result within a median of 19 min (IQR 15–22 min); p < 0.001. The device failure rate for the central laboratory (8 failures, 3.2%) was significantly higher than that of the i-STAT device (1 failure, 0.4%, p = 0.04), but not statistically different than the Triage device (3 failures, 1.2%). Neither the Triage nor the i-STAT were statistically different than the central laboratory result in terms of sensitivity; the i-STAT was less specific than the Triage result (p = 0.003). The area under the curve for the Triage device was 0.95 (95% confidence interval [CI] 0.91–0.98), whereas the area under the curve for the i-STAT device was 0.98 (95% CI 0.96–0.99; p < 0.01).

Conclusions

Both POC devices tested were accurate and rarely failed; however, the i-STAT was faster with single use.     

Remifentanil discontinuation and subsequent intensive care unit-acquired infection: a cohort study

Introduction

The FloTrac/Vigileo? (Edwards Lifesciences, Irvine, CA, USA) allows pulse pressure-derived cardiac output measurement without external calibration. Software modifications were performed in order to eliminate initially observed deficits. The aim of this study was to assess changes in cardiac output determined by the FloTrac/Vigileo? system (FCO) with an initially released (FCOA) and a modified (FCOB) software version, as well as changes in cardiac output from the PiCCOplus? system (PCO; Pulsion Medical Systems, Munich, Germany). Both devices were compared with cardiac output measured by intermittent thermodilution (ICO).

Methods

Cardiac output measurements were performed in patients after elective cardiac surgery. Two sets of data (A and B) were obtained using FCOA and FCOB in 50 patients. After calibration of the PiCCOplus? system, triplicate FCO and PCO values were recorded and ICO was determined in the supine position and cardiac output changes due to body positioning were recorded 15 minutes later (30° head-up, 30° head-down, supine). Student's t test, analysis of variance and Bland-Altman analysis were calculated.

Results

Significant changes of FCO, PCO and ICO induced by body positioning were observed in both data sets. For set A, ΔFCOA was significantly larger than ΔICO induced by positioning the head down. For set B, there were no significant differences between ΔFCOB and ΔICO. For set A, increased limits of agreement were found for FCOA-ICO when compared with PCO-ICO. For set B, mean bias and limits of agreement were comparable for FCOB-ICO and PCO-ICO.

Conclusions

The modification of the FloTrac/Vigileo? system resulted in an improved performance in order to reliably assess cardiac output and track the related changes in patients after cardiac surgery.     

Concordance between point‐of‐care blood gas analysis and laboratory autoanalyzer in measurement of hemoglobin and electrolytes in critically ill patients

Background

We tested the hypothesis that the results of the same test performed on point‐of‐care blood gas analysis (BGA) machine and automatic analyzer (AA) machine in central laboratory have high degree of concordance in critical care patients and that the two test methods could be used interchangeably.

Methods

We analyzed 9398 matched pairs of BGA and AA results, obtained from 1765 patients. Concentration pairs of the following analytes were assessed: hemoglobin, glucose, sodium, potassium, chloride, and bicarbonate. We determined the agreement using concordance correlation coefficient (CCC) and Bland‐Altman analysis. The difference in results was also assessed against the United States Clinical Laboratory Improvement Amendments (US‐CLIA) 88 rules. The test results were considered to be interchangeable if they were within the US‐CLIA variability criteria and would not alter the clinical management when compared to each other.

Results

The median time interval between sampling for BGA and AA in each result pair was 5 minutes. The CCC values ranged from 0.89(95% CI 0.89‐0.90) for chloride to 0.98(95% CI 0.98‐0.99) for hemoglobin. The largest bias was for hemoglobin. The limits of agreement relative to bias were largest for sodium, with 3.4% of readings outside the US‐CLIA variation rule. The number of readings outside the US‐CLIA acceptable variation was highest for glucose (7.1%) followed by hemoglobin (5.9%) and chloride (5.2%).

Conclusion

We conclude that there is moderate to substantial concordance between AA and BGA machines on tests performed in critically ill patients. However, the two tests methods cannot be used interchangeably, except for potassium.

     

Glycated hemoglobin predicts all-cause, cardiovascular, and cancer mortality in people without a history of diabetes undergoing coronary angiography

OBJECTIVE

Glycated hemoglobin has been suggested to be superior to fasting glucose for the prediction of vascular disease and death from any cause. The aim of the present work was to analyze and compare the predictive value of glycated hemoglobin and fasting glucose on all-cause and cause-specific mortality in subjects who underwent coronary angiography.

RESEARCH DESIGN AND METHODS

We studied 2,686 participants of the Ludwigshafen Risk and Cardiovascular health study without a history of diabetes. The majority of this cohort had coronary artery disease. Glycated hemoglobin was measured at the baseline examination. The mean (± SD) duration of the follow-up for all-cause, cardiovascular, and cancer mortality was 7.54 ± 2.1 years.

RESULTS

A total of 508 deaths occurred during the follow-up. Of those, 299 were accounted for by cardiovascular diseases and 79 by cancer. Baseline glycated hemoglobin was predictive of all-cause, cardiovascular, and cancer mortality. The multivariable-adjusted hazard ratios (HR) (95% CI) for glycated hemoglobin values of <5.0, 5.0–5.4, 5.5–5.9, 6.0–6.4, 6.5–7.4, and ≥7.5% for all-cause mortality were 1.36 (0.85–2.18), 1.00 (0.76–1.32), 1.00 (reference), 1.11 (0.88–1.41), 1.39 (1.07–1.82), and 2.15 (1.32–3.53), respectively. Similar J-shaped relationships were found between glycated hemoglobin and cardiovascular and cancer mortality. The associations of glycated hemoglobin with all-cause and cardiovascular mortality remained significant after inclusion of fasting glucose as a covariate. However, fasting glucose was not significantly related to mortality when adjusting for glycated hemoglobin.

CONCLUSIONS

Glycated hemoglobin significantly and independently of fasting glucose predicts all-cause and cardiovascular mortality in whites at intermediate to high cardiovascular risk.The glycated hemoglobin concentration is a measure of the 2–3-month average endogenous exposure to glucose. It has low intraindividual variability and can be determined in the nonfasting state (1). Therefore, glycated hemoglobin is used for the estimation of glucose control in subjects with known diabetes (2,3). Recently, glycated hemoglobin has also been included in the diagnosis algorithm of diabetes because it indicates the risk of microvascular disease (4).Selvin et al. (5) demonstrated in participants of the Atherosclerosis Risk In Communities study who did not have a history of diabetes that glycated hemoglobin was also a strong predictor of future diabetes, cardiovascular disease, and all-cause mortality. In this community-based cohort of middle-aged white and black subjects, the predictive value of glycated hemoglobin was superior to the prognostic information of fasting glucose (5). It was of particular interest that they found a J-shaped association between glycated hemoglobin and death from any cause (5). Compelling explanations for this observation have not been provided. Thus, the authors suggested further exploration of health risks associated with low-normal glycemia and of confounders affecting glycated hemoglobin values.This work aimed to investigate and compare the predictive values of glycated hemoglobin and fasting glucose on all-cause and cardiovascular mortality in whites who underwent coronary angiography. Another objective was to analyze the relationship of glycated hemoglobin with death from cancer. Furthermore, we were interested in metabolic traits and comorbidity associated with low-normal glycemic state that might implicate increased risk of mortality. We studied participants of the Ludwigshafen Risk and Cardiovascular (LURIC) health study without a history of diabetes (6). The majority of this cohort had coronary artery disease (CAD) (6).     

Factors related to the acceptance of home care and nursing homes among older Egyptians: A cross-sectional study

Background

Socio-demographic changes may deprive older Egyptians from receiving care by family members and raise the question of how they react if they become dependent on help.

Objective

The objective of this study was to determine factors related to the acceptance of home care and nursing homes among older Egyptians.

Design

A two group comparative design based on self-reports.

Participants

The sample was composed of 344 older persons receiving home care or staying in a nursing home and 267 non-care recipients.

Setting

The study was conducted in Greater Cairo.

Methods

Factors related to the acceptance of home care and nursing homes were determined separately for each group by logistic regression.

Results

Lesser feelings of shame while receiving care from non-family members were related to an increased acceptance of both kinds of care. For non-care recipients disagreement to the traditional idea of family care had a similar effect. For care recipients the experience made with a particular kind of care was strongly related to its acceptance.

Discussion

Home care is a new phenomenon in Cairo and in contrast to nursing homes it was unknown to most study participants. For this reason any conclusion about which kind of service is preferred by older Egyptians would be a premature one.

Conclusion

Feelings of shame while receiving care from a non-family member are more important than functional limitations when older Egyptians are considering the options of home care and nursing homes.     

Utility of point-of-care testing in ED triage

Background

Triage systems are commonly used in emergency departments (ED) to prioritize patients. Laboratory testing is not typically used to help risk-stratify patients at triage.

Objectives

We studied the utility of point-of-care (POC) testing at triage in ED patients with high-risk complaints.

Methods

We conducted a prospective observational study on a convenience sample of ED patients at an urban academic hospital with 60,000 annual visits. Patients who were triaged to the waiting area with any of the following criteria were approached for enrollment: (1) chest pain or shortness of breath in patients older than 40 years, (2) possible infection in the presence of two or more systemic inflammatory response system criteria in patients older than 18 years, and (3) patients > 65 years with non-traumatic complaints. A total of 300 subjects were enrolled. All enrolled patients received POC testing that included a combination of Chem8+, hemoglobin, troponin, B-type natriuretic peptide, and lactate. The triage nurse completed a survey after receiving the results.

Results

POC results was reported to be helpful in 56% of patients, changed the triage level in 15% of patients and led to 6% of patients being brought back for rapid physician evaluation. Overall, 50% of patients had one or more abnormal POC laboratory tests. There was no relationship between ED census and the likelihood of being helpful, changing the triage level, changing management, or bringing patients back any faster.

Conclusion

POC testing at triage is a helpful adjunct in triage of patients with high-risk ED complaints.     

Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study

OBJECTIVE

Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up.

RESEARCH DESIGN AND METHODS

The randomized double-blind clinical trial of metformin or placebo followed by a 7–8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference.

RESULTS

No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 ± 5.65% vs. 0.02 ± 5.52%, P < 0.001, and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001).

CONCLUSIONS

Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.Metformin is an established treatment for diabetes with a good safety profile (1). Its most common side effects are gastrointestinal (1). These symptoms are generally transient, resolve spontaneously, and can often be avoided by gradual escalation of dosage. Metformin treatment has not been associated with hypoglycemia unless used in conjunction with other glucose-lowering medicines (sulfonylureas or insulin). In U.S. clinical trials, about 4% of participants were unable to continue metformin due to adverse effects. Serious adverse events are infrequent and generally limited to lactic acidosis, which occurs only in persons with renal or hepatic insufficiency or other contraindications. Metformin is associated with weight loss when used to treat diabetes and thus differs from a number of other antidiabetic medications that are associated with weight stability or gain (2,3). To date, metformin is indicated only for diabetes management and not for weight loss in individuals with or without diabetes.In the Diabetes Prevention Program (DPP), metformin reduced the development of diabetes by 31% over an average of 2.8 years of follow-up (4,5). The long-term follow-up of the DPP, the DPP Outcomes Study (DPPOS), included an open-label extension of metformin treatment in those randomly assigned to metformin in the DPP. After a median of 10 years of follow-up since DPP randomization, both the lifestyle and metformin intervention groups had significantly less diabetes than the placebo group (6). During the DPP, participants randomized to metformin experienced an average 2.1-kg weight loss (4). Weight loss was a strong predictor of diabetes prevention in both the metformin and placebo groups with weight loss accounting for 64% of the metformin versus placebo effect on diabetes prevention (7). Weight loss in the metformin group was maintained throughout the combined DPP and DPPOS period with metformin participants having an average 2.5-kg weight loss over time (6). This report updates these findings by documenting the long-term safety and tolerability of metformin, and in a post hoc analysis, it tests the hypothesis that greater adherence to metformin is associated with greater weight loss and reduction in waist circumference in participants randomly assigned to metformin compared with those randomly assigned to placebo.     

Accuracy of bedside point of care testing in critical emergency department patients

Background

Point-of-care (POC) testing reduces laboratory turn-around having the potential to improve timely diagnosis and management. We compared the accuracy of nurse performed POC and core laboratory testing and determined whether deviations between the two were clinically meaningful.

Cluster-randomized trial of a mobile phone personalized behavioral intervention for blood glucose control

OBJECTIVE

To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with standard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A cluster-randomized clinical trial, the Mobile Diabetes Intervention Study, randomly assigned 26 primary care practices to one of three stepped treatment groups or a control group (usual care). A total of 163 patients were enrolled and included in analysis. The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period. Secondary outcomes were changes in patient-reported diabetes symptoms, diabetes distress, depression, and other clinical (blood pressure) and laboratory (lipid) values. Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support. Patients received automated, real-time educational and behavioral messaging in response to individually analyzed blood glucose values, diabetes medications, and lifestyle behaviors communicated by mobile phone. Providers received quarterly reports summarizing patient’s glycemic control, diabetes medication management, lifestyle behaviors, and evidence-based treatment options.

RESULTS

The mean declines in glycated hemoglobin were 1.9% in the maximal treatment group and 0.7% in the usual care group, a difference of 1.2% (P < 0.001) over 12 months. Appreciable differences were not observed between groups for patient-reported diabetes distress, depression, diabetes symptoms, or blood pressure and lipid levels (all P > 0.05).

CONCLUSIONS

The combination of behavioral mobile coaching with blood glucose data, lifestyle behaviors, and patient self-management data individually analyzed and presented with evidence-based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year.Diabetes affects 38 million people in the U.S.; 40% are undiagnosed, and another 87 million are considered prediabetic. Costs exceed $100 billion annually (1,2). Changes in lifestyle/self-care behaviors, complex medical regimens, use of glucose-testing devices, and frequent data assessment by patients and providers are required to improve blood glucose and subsequent outcomes. In clinical trials, better self-care/lifestyle resulted in better diabetes outcomes (3–5). However, these clinical trials improved outcomes for circumscribed patient populations (6–9). Patients with diabetes are diverse, treatment may involve multiple specialists, and care by primary care providers (PCPs) is limited to 15-min visits. Only 55% of individuals with type 2 diabetes receive diabetes education (10); 16% report adhering to recommended self-management activities (11). Concern that elevated blood glucose levels result in microvascular comorbidity motivates behavioral change and monitoring interventions to assist patients and PCPs (12–14). The Mobile Diabetes Intervention Study, reported here, evaluated a diabetes-coaching system, using mobile phones and patient/provider portals for patient-specific treatment and communication. The hypothesis tested was that mobile telephone feedback on self-management of blood glucose results and lifestyle and clinical management offered to patients with type 2 diabetes and their providers can reduce glycated hemoglobin levels over 1 year.     

Differential interferences of hemoglobin and hemolysis on insulin assay with the Abbott Architect®-Ci8200 immunoassay

Objectives

This paper evaluates the effect of hemoglobin (Hb) and hemolysis on insulin measurements with the Architect®-Ci8200 analyzer.

Design and methods

Insulin concentrations were measured using the Architect®-Ci8200. Interference studies were performed by spiking serum pools of defined insulin concentrations with increasing concentrations of either free Hb or hemolysate. A change of more than 10% was taken as evidence of significant interference.

Results

A significant negative bias in insulin results was observed only in samples spiked with hemolysate but not with free Hb. The bias was proportional to the degree of hemolysis and to the time elapsed before insulin assay. This interference was decreased when samples were kept at + 4 °C.

Conclusions

For all insulin requests, hemolysis must be systematically checked before biological interpretation of insulin results.     

An analysis of discrepancy between point-of-care and central laboratory international normalized ratio testing in ED patients with cerebrovascular disease

Objective

Our objective was to identify demographic, clinical, and operational variables associated with discrepancy between point-of-care (POC) and central laboratory international normalized ratio (INR) results in emergency department (ED) patients with acute cerebrovascular disease.

Methods

We conducted a retrospective, observational cohort study of a series of 637 patients with acute cerebrovascular disease over 30 months who underwent simultaneous POC, using the i-STAT POC analyzer (Abbott, Princeton, NJ), and central laboratory INR testing at ED presentation. Point-of-care INR results greater than ± 0.25 INR units from the central laboratory INR value were considered discrepant. We analyzed potential predictors of POC INR discrepancy from demographic, clinical, and operational variables using multivariable logistic regression. We evaluated the change in POC INR discrepancy incidence over the study interval using analysis of variance methodology.

Results

The final diagnoses of the 637 subjects were acute ischemic stroke (n = 427), transient ischemic attack (n = 105), and intracranial hemorrhage (n = 105). Discrepant POC INR results occurred in 21.5% (137/637) of subjects. The mean bias between POC and central laboratory INR was 0.24 ± 0.69 (range, 0-11.3). Significant covariates of POC INR discrepancy were oral anticoagulant use (odds ratio, 3.03; confidence interval, 1.37-6.68) and increasing activated partial thromboplastin time (aPTT) (odds ratio, 1.07; confidence interval, 1.02-1.12). We observed a significant reduction trend in the incidence of POC-central laboratory discrepancy over the study period, decreasing on average at 0.42% per month (F = 5.59, P = .025).

Conclusion

In this retrospective study, oral anticoagulant use and increasing aPTT were significantly associated with POC INR discrepancy in ED patients with acute cerebrovascular disease. Point-of-care INR discrepancy incidence decreased over the study interval.     

The Effect of Iron and Erythropoietin Treatment on the A1C of Patients With Diabetes and Chronic Kidney Disease

OBJECTIVE

To examine the effect of intravenous iron and erythropoietin-stimulating agents (ESAs) on glycemic control and A1C of patients with diabetes and chronic kidney disease (CKD).

RESEARCH DESIGN AND METHODS

This was a prospective study of patients with type 2 diabetes and CKD stage IIIB or IV undergoing intravenous iron (group A) and/or ESA (group B). Full blood profiles were determined over the study period. Glycemic control was monitored using A1C, seven-point daily glucose three times weekly, and continuous glucose monitoring (CGM).

RESULTS

There were 15 patients in both group A and group B. Mean A1C (95% CI) values fell in both groups (7.40% [6.60–8.19] to 6.96% [6.27–7.25], P < 0.01, with intravenous iron and 7.31% [6.42–8.54] to 6.63% [6.03–7.36], P = 0.013, ESA). There was no change in mean blood glucose in group A (9.55 mmol/l [8.20–10.90] vs. 9.71 mmol/l [8.29–11.13], P = 0.07) and in group B (8.72 mmol/l [7.31–10.12] vs. 8.78 mmol/l [7.47–9.99], P = 0.61) over the study period. Hemoglobin and hematocrit values significantly increased following both treatments. There was no linear relationship found between the change in A1C values and the rise of hemoglobin following either treatment.

CONCLUSIONS

Both iron and ESA cause a significant fall in A1C values without a change to glycemic control in patients with diabetes and CKD. At the present time, regular capillary glucose measurements and the concurrent use of CGM remain the best alternative measurements of glycemic control in this patient group.A1C is the most widely accepted and used method of assessing chronic glycemia in patients with diabetes. It is formed by the irreversible binding of glucose to hemoglobin over the lifespan of the erythrocyte (1,2).Patients with chronic kidney disease (CKD) are commonly anemic due to a variety of reasons, including functional or absolute iron deficiency and erythropoietin insufficiency (3,4). Treatment of anemia in patients with CKD using iron replacement therapy and erythropoietin-stimulating agents (ESAs) has resulted in significant improvements to quality of life and the correction of anemia without the need for blood transfusions (3–5).There are several studies (6–9) that show a fall of A1C in patients treated with ESA and iron therapy. These studies are mostly in patients already receiving hemodialysis and those without diabetes. The effect of the lowering of the A1C values following either treatment has been postulated to be secondary to the formation of new erythrocytes in the blood stream, causing a change of proportion of young to old cells, and also from an alteration in the red-cell glycation rates (10,11).Despite this, a comprehensive analysis of the relationship between glycemic control and A1C changes in patients undergoing both iron and ESA therapy has never been performed using robust methods, such as seven-point daily capillary glucose monitoring (7PGM) or using CGM devices. Thus, any class effect that iron therapy and ESA may have on A1C values could in fact represent a parallel change to glycemic control along with the currently postulated physiological changes. Furthermore, the effect of the fall in A1C following these two therapies has not been well studied in patients not already on hemodialysis.This study therefore sought to establish how intravenous iron and ESA therapy influence A1C values in patients with type 2 diabetes and CKD not on hemodialysis. Robust monitoring of blood glucose was performed throughout the study period to determine if the anticipated fall in A1C was a true reflection of glycemic control.     

Retinol-binding protein 4 is associated with prediabetes in adults from the general population: the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study

OBJECTIVE

We examined the association between retinol-binding protein 4 (RBP4), a novel adipokine, and prediabetes (isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT], and combined IFG and IGT) in men and women aged 32–81 years.

RESEARCH DESIGN AND METHODS

The analysis was based on 2,614 participants without previously diagnosed diabetes and those with newly diagnosed diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study, conducted from 2006 to 2008 in southern Germany. Plasma RBP4 was analyzed by immunonephelometry.

RESULTS

In logistic regression analysis, RBP4 levels in the fourth quartile versus the first quartile were significantly associated with prediabetes (i-IGT, i-IFG, and IFG/IGT; reference normal glucose tolerance) independent of known metabolic risk factors and lifestyle variables (odds ratio 1.63 [95% CI 1.17–2.27] after multivariable adjustment). Stratification by sex showed generally similar results.

CONCLUSIONS

RBP4 levels were associated with prediabetes in individuals from the general population. Prospective studies investigating the impact of RBP4 on the development of glucose intolerance are needed.Retinol-binding protein 4 (RBP4), the specific transport protein for retinol (vitamin A) in the blood (1), is a novel adipokine that is secreted from adipocytes and hepatocytes. Although studies in mice have suggested that elevated RBP4 levels may play a causal role in the development of insulin resistance and type 2 diabetes, previous studies in humans on this issue are controversial (2–5). Most studies investigating this association so far were based on very small sample sizes (2,6) and on groups at high risk of insulin resistance and future development of type 2 diabetes (7,8). To date, no population-based data are available to determine whether RBP4 influences the risk for prediabetes. Therefore, the current study set out to investigate the possible association between RBP4 levels and prediabetic groups (isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT], and combined IFG and IGT) in a population of men and women aged 32–81 years in southern Germany.