Cultural and clinical effectiveness of the 'QAAMS' point-of-care testing model for diabetes management in Australian aboriginal medical services

The national Quality Assurance for Aboriginal Medical Services (QAAMS) Program, in which point-of-care testing (POCT) for haemoglobin A(1c) (HbA(1c)) and urine albumin: creatinine ratio (ACR) is performed for diabetes management in 65 Australian Aboriginal medical services, is now embedded in the practice of diabetes care across Indigenous Australia. This paper documents the results of a detailed survey to assess levels of satisfaction with the QAAMS HbA(1c) Program among three key stakeholder groups-doctors, POCT operators and patients with diabetes. Both doctors and patients with diabetes agreed that the immediacy of POCT results contributed positively to patient care, improved the doctor-patient relationship, and made the patient more likely to be both compliant and self-motivated to improve their diabetes control. Both POCT operators and patients with diabetes reported improved satisfaction with their diabetes services after the introduction of POCT. The paper also provides evidence from two participating medical services that POCT has been an effective tool in improving the delivery of pathology services and clinical outcomes for both individuals and groups of patients with diabetes. A statistically significant reduction in HbA(1c) from 9.3% (+/- 2.0) to 8.6% (+/- 2.0) was observed in 74 diabetes patients 12 months after commencing POCT (p = 0.003, paired t-test). An improvement in the percentage of patients achieving glycaemic targets and a reduction in the percentage of patients with poor control was also observed in this group. These data provide evidence that the QAAMS POCT model delivers a culturally and clinically effective service for diabetes management in Aboriginal Australia.     

Results of an innovative education, training and quality assurance program for point-of-care HbA1c testing using the Bayer DCA 2000 in Australian Aboriginal Community Controlled Health Services

This study describes the development, implementation and management of a multi-faceted quality assurance program called Quality Assurance for Aboriginal Medical Services (QAAMS) to support point-of-care HbA(1c) testing on the Bayer DCA 2000 in Aboriginal people with diabetes from 45 Australian Aboriginal Community Controlled Health Services.THE QUALITY ASSURANCE PROGRAM COMPRISED FOUR ELEMENTS: production of culturally appropriate education resources, formal training for Aboriginal Health Workers conducting HbA(1c) testing, an external quality assurance program and on-going quality management support services including a help hotline and an annual workshop. Aboriginal Health Workers were required to test two quality assurance (QAAMS) samples in a blind sense every month since July 1999. Samples were linearly related and comprised six paired levels of HbA(1c). The short and long term performance of each service's DCA 2000 was reviewed monthly and at the end of each six month testing cycle.The average participation rate over 7 six-monthly QAAMS testing cycles was 88%. 84% of 3100 quality assurance tests performed were within preset limits of acceptability. The median precision (CV%) for HbA(1c) testing has averaged 3.8% across the past 5 cycles (range 3.4 to 4.0%) and is continuing to improve. The introduction of a medical rebate for HbA(1c) testing has ensured the program's sustainability.Through continuing education and training, Aboriginal Health Workers have achieved consistent analytical performance for HbA(1c) testing on the DCA 2000, equivalent to that of laboratory scientists using the same instrument. This unique quality assurance model can be readily adapted to other Indigenous health settings and other point-of-care tests and instruments.     

The National QAAMS Program – A Practical Example of PoCT Working in the Community

The Quality Assurance for Aboriginal and Torres Strait Islander Medical Services (QAAMS) Program is the largest and longest-standing national point-of-care testing (PoCT) program in Australia. With a focus on PoCT for diabetes management, it now operates in 115 Indigenous medical services and has been funded continuously by the Australian Government for 11 years. A recent independent evaluation of the QAAMS Program concluded that the program continues to meet best practice standards for Indigenous healthcare, diabetes management and PoCT.     

Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes: The ADD-CKD Study (Awareness,Detection and Drug Therapy in Type 2 Diabetes and Chronic Kidney Disease)

This US, multicenter, observational study assessed the CKD prevalence in adult patients with type-2 diabetes mellitus (T2DM) and characterized the proportion of detected and undiagnosed CKD in the primary care setting using the following: a clinician survey; a patient physical exam and medical history; a single blood draw for estimated glomerular filtration rate (eGFR) and glycosolated hemoglobin (HbA1c); urine dipstick for protein; urine albumin-creatinine ratio (ACR); two patient quality of life questionnaires; and a 15-month medical record review. The study consisted of 9339 adults with T2DM and 466 investigator sites. Of the 9339 enrolled, 9307 had complete data collection for analysis. The 15-month retrospective review showed urine protein, urine ACR, and eGFR testing were not performed in 51.4%, 52.9% and 15.2% of individuals, respectively. Of the 9307 patients, 5036 (54.1%) had Stage 1–5 CKD based on eGFR and albuminuria; however, only 607 (12.1%) of those patients were identified as having CKD by their clinicians. Clinicians were more successful in diagnosing patients with Stage 3–5 CKD than Stages 1 and 2. There were no differences in clinicians’ likelihood of identification of CKD based on practice setting, number of years in practice, or self-reported patients seen per week. Awareness or patient self-reported CKD was 81.1% with practitioner detection versus 2.6% in the absence of diagnosis. Primary care of T2DM demonstrates recommended urine CKD testing is underutilized, and CKD is significantly under-diagnosed. This is the first study to show CKD detection is associated with awareness.     

Reduction in urine C-peptide clearance rate after metabolic control in NIDDM patients

One hour urine C-peptide and creatinine clearance rates were determined simultaneously in 25 hospitalized patients with non-insulin-dependent diabetes mellitus (NIDDM) undergoing sulfonylurea and/or diet treatment. The studies had been performed after an overnight fast on the second day of admission and on a day soon before discharge, with intervals of 18.9 +/- 7.0 days. Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) values decreased significantly at the second examination as compared to the initial values (FPG: 101 +/- 20 mg/dl vs. 161 +/- 47 mg/dl, p less than 0.005; HbA1c: 7.3 +/- 1.5% vs. 8.4 +/- 1.7%, p less than 0.005). The urine C-peptide clearance rate also decreased significantly after metabolic control (0.75 +/- 0.36 l/hr vs. 1.06 +/- 0.54 l/hr, p less than 0.005). Meanwhile, the urine creatinine clearance rate tended to decrease, but the difference was not significant (3.69 +/- 2.04 l/hr vs. 4.87 +/- 2.98 l/hr) at the second examination. The data suggest that the urine C-peptide clearance rate is susceptible to the effects of the fluctuation of metabolic states in NIDDM patients. In order to use urinary C-peptide for a follow up study of pancreatic B-cell secretion, the changes in C-peptide clearance under various metabolic conditions must be taken into account.     

A longitudinal study examining adherence to guidelines in diabetes care according to different definitions of adequacy and timeliness

Background

Performance indicators assessing quality of diabetes care often look at single processes, e.g. whether an HbA1c test was conducted. Adequate care, however, consists of consecutive processes which should be taken in time (clinical pathways). We assessed quality of diabetes care by looking at single processes versus clinical pathways. In addition, we evaluated the impact of time period definitions on this quality assessment.

Methodology

We conducted a cohort study in 2007–2008 using the GIANTT (Groningen Initiative to Analyse type 2 diabetes Treatment) database. Proportions of patients adequately managed for HbA1c, systolic blood pressure (SBP), LDL-cholesterol (LDL-C), and albumin/creatinin ratio (ACR) were calculated for the pathway of (1) risk factor level testing, (2) treatment intensification when indicated, (3) response to treatment evaluation. Strict and wide time periods for each step were defined. Proportions of patients adequately managed regarding the overall pathway and single steps, using strict or wide time periods were compared using odds ratios (OR) with 95% confidence intervals.

Findings

Of 11176 patients diagnosed with type 2 diabetes, 9439 with complete follow-up were included. The majority received annual examination of HbA1c (86%) and SBP (86%), whereas this was 67% for LDL-C and 49% for ACR. Adequate management regarding the three-step pathway was observed in 73%, 53%, 46%, 41% of patients for HbA1c, SBP, LDL-C, and ACR respectively. Quality scores reduced significantly due to the second step (OR 0.43, 0.18, 0.44, 0.74), but were not much further reduced by the third step. Timely treatment evaluation occurred in 88% for HbA1c, 87% for SBP, 83% for LDL-C, and 76% for ACR. The overall score was not significantly changed by using strict time windows.

Conclusion

Quality estimates of glycemic, blood pressure and cholesterol management are substantially reduced when looking at clinical pathways as compared to estimates based on commonly used simple process measures.     

Evaluation of four hematology and a chemistry portable benchtop analyzers using non-human primate blood

Background  Near patient testing (NPT) and point-of-care testing (POCT) using portable benchtop analyzers has become necessary in many areas of the medical community, including biocontainment.
Methods  We evaluated the Beckman AcT diff, Abaxis Vetscan HMII (two instruments), Abbott Cell-Dyn 1800, and Abaxis Vetscan VS2 for within-run precision and correlation to central laboratory instruments using non-human primates blood.
Results  Compared with the central laboratory instruments, the Beckman AcT diff correlated on 80%; the HMII instruments on 31% and 44%, the CD1800 on 31%, and the VS2 on 71% of assays. For assays with published manufacturers precision guidelines, the AcT diff met all nine, the HMII instruments met one and six of six, and the CD 1800 met one of six.
Conclusions  Laboratories using NPT/POCT must test their individual instruments for precision and correlation, identify assays that are reliable, and exclude or develop supplemental procedures for assays that are not.     

Myocardial Dysfunction in Early Diabetes Patients with Microalbuminuria: A 2-Dimensional Speckle Tracking Strain Study

The aim of this study was to assess myocardial dysfunction in primary diabetes patients with microalbuminuria by 2-dimensional speckle tracking strain. Sixty-two patients with diabetes with or without hypertension and 37 matched hypertension controls were consecutively recruited from January 2011 to 2013. Routine physical examinations, laboratory tests, and echocardiography were performed in all patients. Subjects enrolled were divided into three groups according to history and urine albumin/creatinine ratio (ACR): group I: patients with only hypertension and normoalbuminuria (ACR < 30 mg/g), group II: patients with both hypertension and diabetes and normoalbuminuria (ACR < 30 mg/g), and group III: patients with both hypertension and diabetes and microalbuminuria (ACR 30–300 mg/g). Echocardiographic images of three cardiac cycles were acquired for off-line analysis using the GE EchoPAC software. Indices of cardiac function, including longitudinal, radial and circumferential strains, torsion, and left ventricular ejection fraction (LVEF) were assessed. Statistical analysis was performed using SPSS 13.0. Finally, 56 subjects and 32 controls were included in the analyses. There was no significant difference in age, gender, heart rate, BMI, and LVEF among groups, except for the blood pressure, ACR, and HbA1c. E wave, A wave, EDT, E _m, and E/E _m in group III were different with those in group I. Mean longitudinal strain (mSL), average SL of six segments in 4-chamber apical view (SL₄) decreased obviously. The peak circumferential strain decreased in group III, while the torsion was compensatively increased. ACR was negatively related to mSL, SL₄, E/E _m, and positively related to torsion. We deduced that ACR maybe a predictor for myocardial damage in primary diabetes.     

FINDRISK questionnaire combined with HbA1c testing as a potential screening strategy for undiagnosed diabetes in a healthy population

Despite the efforts to control the epidemic of diabetes the total number of people living with diabetes is still steadily rising. In order to detect people at risk, cost-effective, convenient, and sensitive screening tools to assess the diabetes risk and to detect undiagnosed type 2 diabetes need to be developed and implemented in the primary care setting. To evaluate the combination of the well established FINDRISK questionnaire and HbA1c testing as a potential screening strategy the data obtained from 671 blood donors were analyzed for a potential correlation with the results of an oral glucose tolerance test. Based on the oral glucose tolerance test, 65 blood donors (9.7%) were newly diagnosed with diabetes, 336 (50.1%) with prediabetes, and 270 (40.2%) had a normal test result. Of the 401 blood donors diagnosed with prediabetes or diabetes 322 (80.3%) had a HbA1c between 5.7% and 6.4% and 27 (6.7%) with a HbA1c of 6.5% or greater. The majority of the blood donors newly diagnosed with diabetes or prediabetes (n=327) had a FINDRISK result of 12 points or higher. ROC analyses confirmed that the optimal cut off levels were for FINDRISK ≥ 12 points and for HbA1c ≥ 5.9%. Thus, a 3-step screening strategy applying the FINDRISK questionnaire followed by HbA1c testing and performing an oral glucose tolerance test on selected individuals could be a cost-saving approach for screening large populations and identifying people at risk for diabetes or undiagnosed diabetes.     

Liquid chromatography-based determination of urinary free and total N(epsilon)-(carboxymethyl)lysine excretion in normal and diabetic subjects

We propose a specific, reproducible and sensitive HPLC method for the determination of N(epsilon)-(carboxymethyl)lysine (CML) excreted in urine. Total CML was measured in acid hydrolysates of urine samples, while free CML was measured in acetonitrile-deproteinised urine samples using a RP-HPLC method with ortho-phtaldialdehyde (OPA)-derivatisation and fluorescence detection suited for automation. We compared the CML excretion of 51 non-proteinuric patients with diabetes mellitus (DM) (age 57+/-14 years, HbA1c 8.0+/-1.8%) to 42 non-diabetic controls (C) (age 45+/-17 years). The urinary excretion of total CML in diabetic patients was increased by approximately 30% (DM: 0.58+/-0.21; C: 0.45+/-0.14 microM/mmol creatinine; P<0.001). While urinary excretion of free CML was not significantly different, excretion of bound CML was increased (DM: 0.36+/-0.17; C: 0.27+/-0.14; P<0.05) in diabetic patients. CML excretion was correlated with protein and albumin excretion, but did not correlate with HbA1c, duration of DM or diabetic complications such as neuropathy or retinopathy. Furthermore, no age-dependent change of total CML excretion was found, while free CML excretion was lower in younger subjects. The specific and sensitive determination of CML by RP-HPLC of its OPA-derivative is well suited for automation and better than that of less defined glycoxidation products (AGEs).     

Extreme Levels of HbA1c Increase Incident ESRD Risk in Chinese Patients with Type 2 Diabetes: Competing Risk Analysis in National Cohort of Taiwan Diabetes Study

Background

Whether HbA1c is a predictor of end-stage renal disease (ESRD) in type 2 diabetes patients remains unclear. This study evaluated relationship between HbA1c and ESRD in Chinese patients with type 2 diabetes.

Methods

Patients aged ≥ 30 years who were free of ESRD (n = 51 681) were included from National Diabetes Care Management Program from 2002–2003. Extended Cox proportional hazard model with competing risk of death served to evaluate association between HbA1c level and ESRD.

Results

A total of 2613 (5.06%) people developed ESRD during a follow-up period of 8.1 years. Overall incidence rate of ESRD was 6.26 per 1000 person-years. Patients with high levels of HbA1c had a high incidence rate of ESRD, from 4.29 for HbA1c of  6.0%–6.9% to 10.33 for HbA1c ≥ 10.0% per 1000 person-years. Patients with HbA1c < 6.0% particularly had a slightly higher ESRD incidence (4.34 per 1000 person-years) than those with HbA1c  of 6.0%–6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c < 6.0% and ≥ 10.0% exhibited an increased risk of ESRD (HR: 1.99, 95% CI: 1.62–2.44; HR: 4.42, 95% CI: 3.80–5.14, respectively) compared with those with HbA1c of 6.0%–6.9%.

Conclusions

Diabetes care has focused on preventing hyperglycemia, but not hypoglycemia. Our study revealed that HbA1c level ≥ 7.0% was linked with increased ESRD risk in type 2 diabetes patients, and that HbA1c < 6.0% also had the potential to increase ESRD risk. Our study provides epidemiological evidence that appropriate glycemic control is essential for diabetes care to meet HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy.     

Plasma protein advanced glycation end products, carboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes

In Diabetes Mellitus (DM), glucose and the aldehydes glyoxal and methylglyoxal modify free amino groups of lysine and arginine of proteins forming advanced glycation end products (AGEs). Elevated levels of these AGEs are implicated in diabetic complications including nephropathy. Our objective was to measure carboxymethyl cysteine (CMC) and carboxyethyl cysteine (CEC), AGEs formed by modification of free cysteine sulfhydryl groups of proteins by these aldehydes, in plasma proteins of patients with diabetes, and investigate their association with the albumin creatinine ratio (ACR, urine albumin (mg)/creatinine (mmol)), an indicator of nephropathy. Blood was collected from forty-two patients with type 1 and 2 diabetes (18–36 years) and eighteen individuals without diabetes (17–35 years). A liquid chromatography-mass spectrophotometric method was developed to measure plasma protein CMC and CEC levels. Values for ACR and hemoglobin A1C (HbA1C) were obtained. Mean plasma CMC (μg/l) and CEC (μg/l) were significantly higher in DM (55.73 ± 29.43, 521.47 ± 239.13, respectively) compared to controls (24.25 ± 10.26, 262.85 ± 132.02, respectively). In patients with diabetes CMC and CEC were positively correlated with ACR, as was HbA1C. Further, CMC or CEC in combination with HbA1C were better predictors of nephropathy than any one of these variables alone. These results suggest that glucose, glyoxal, and methylglyoxal may all be involved in the etiology of diabetic nephropathy.     

Effect of long-term Helicobacter felis infection in a mouse model of streptozotocin-induced diabetes

BACKGROUND: We previously REPORTED that mice with diabetes and short-term Helicobacter felis infection had an increase in glycated hemoglobin (HbA1c). Here we report the effect of long-term infection. MATERIALS AND METHODS: Six-week-old C57BL/6 mice were injected with streptozotocin to induce diabetes and started on daily insulin. Following streptozotocin injection, animals were paired according to their HbA1c values and randomized to orally receive either H. felis or culture medium alone. Weight and HbA1c were monitored monthly for 6 months. RESULTS: Thirty animals corresponding to 15 pairs were included in the study. H. felis-infected diabetic mice developed significantly more gastritis than uninfected animals. Sixteen mice died during the observation period. As compared to uninfected animals, infected mice died more frequently (40% versus 67%, p = .14) and earlier (160 versus 61 days, p = .20); both variables combined showed that H. felis infection significantly decreased the chances of survival during the study period (p = .045). In addition, infected mice showed a trend for higher increase in their HbA1c (0.97 +/- 2.5% versus - 0.22 +/- 3.0%; p = .21) and lower weight gain (2.0 +/- 3.4 g versus 2.9 +/- 2.0 g; p = .15) than uninfected mice. CONCLUSION: Long-term H. felis infection had a deleterious effect in mice with streptozotocin-induced diabetes resulting in increased mortality. If the same phenomenon occurs in humans this could lead to interventions to improve the long-term outcome of patients with diabetes.     

Beta cell response to a mixed meal in nigerian patients with type 2 diabetes

ABSTRACT: BACKGROUND: The pathophysiology of type2 diabetes involves both insulin resistance and poor beta cell function. Studies have been done in several populations to assess the relative importance of these mechanisms in individual patients. In our environment studies to assess beta cell function have been done with glucagon stimulation or an oral glucose tolerance test. This study was done to assess the response of the beta cell to a standardized mixed meal and its relationship with glycaemic control in patients with type2 diabetes. METHODS: Ninety patients with type 2 diabetes were recruited into the study. Weight, height, body mass index and waist circumference were measured. Blood samples were analysed for fasting plasma glucose (FPG) and fasting C peptide (FCP) and glycated haemoglobin (HbA1c). Patients were given their usual drugs for management of their diabetes and then served with a standard meal calculated to contain 50 g of carbohydrate, made up of 53 % carbohydrate, 17 % of protein and 30 % of lipids, providing 500 kcal. Blood samples 2 hours after the start of the meal were analysed for postprandial glucose (PPG) and postprandial C peptide (PCP). Fasting (M0) and postprandial beta cell responsiveness (M1) were calculated. RESULTS: The mean FPG and PPG were 7.51+/ 3.39 mmol/l and 11.02+/4.03 mmol/l respectively while the mean glycated haemoglobin (HbA1c) was 9.0+/2.5 %. The mean fasting C peptide was 1.44+/1.80ug/ml. Many of the patients (56.7 %) had low FCP levels. The mean postprandial C peptide was 4.0+/2.8 ng/ml. There were significant correlations between M1, HbA1c and PPG (p = 0.015, 0.024, 0.001 respectively) and also between M0, HbA1c, PPG and FPG (p = 0.001, 0.002, 0.001). HbA1c decreased across increasing tertiles of M0 (p < 0.001) and also M1 (p = 0.002). In step-wise linear regression analysis, M0 and M1 significantly predicted HbA1c. CONCLUSIONS: Many of the patients had low C peptide levels with poor beta cell response to the meal. The patients had poor glycaemic control and poor beta cell function. Both fasting and postprandial beta cell responsiveness were significant determinants of blood glucose and glycated haemoglobin levels. It is likely that putting these patients on insulin may have led to better glycaemic control in them.     

Opportunistic Screening For Diabetes And Prediabetes Using Hemoglobin A1C In An Urban Primary Care Setting

Objective: In 2010, the American Diabetes Association (ADA) endorsed hemoglobin A1c (HbA1c) as 1 of 3 tests for diabetes and prediabetes screening. We describe the use of HbA1c testing for screening during routine visits in primary care clinics of an urban health care system in the U.S.Methods: In 2013 to 2014, retrospective analyses of deidentified electronic health records over a 2-year period, January 2010 to December 2011, for academic private practices (clinic group 1) and federally-qualified Community Health Centers (clinic group 2) identified 11,885 adults without prior diabetes or recent HbA1c testing. We estimated the proportion of patients eligible for screening according to ADA and U.S. Preventative Services Task Force (USPSTF) guidelines and calculated the potential yield of previously undiagnosed diabetes or prediabetes among those who received at least 1 HbA1c test.Results: Overall, 3,316 and 5,613 patients of clinic groups 1 and 2 (75.2% of each) were eligible for screening by ADA guidelines, while only 1,764 (39.9%) of clinic group 1 and 3,799 (50.9%) of clinic group 2 were eligible by USPSTF guidelines. In those eligible by either guideline, 731 (21.4%) patients of clinic group 1 and 1,293 (21.5%) of clinic group 2 received HbA1c testing; among these, in 71 (9.7%) and 121 (9.4%) patients from clinic groups 1 and 2, respectively, HbA1c results were in the diabetes range, and in 330 (45.2%) and 733 (56.7%), results were in the prediabetes range.Conclusion: In urban primary care settings, appropriate HbA1c testing could result in the detection of a substantial number of previously undiagnosed diabetes and prediabetes cases needing treatment.Abbreviations:ADA = American Diabetes AssociationBMI = body mass indexCI = confidence intervalEHR = electronic health recordHbA1c = hemoglobin A1cHTN = hypertensionICD = International Classification of DiseasesIFCC = International Federation of Clinical ChemistryOGTT = oral glucose tolerance testUSPSTF = U.S. Preventative Services Task Force     

Electrochemical detection of HbA1c, a marker [correction of maker] for diabetes, using a flow immunoassay system

An on-chip electrochemical flow immunoassay system for the detection of hemoglobin A1c (HbA1c) was developed using anti-human hemoglobin (Hb) IgG labeled with ferrocene monocarboxylic acid (Fc-COOH) and boronate-affinity chromatography. An on-chip column packed with boronate-activated agarose beads was used for the separation of HbA1c from both non-glycated Hb and free antibody. Anti-human Hb IgG conjugated to Fc-COOH (Fc-IgG) was used for the electrochemical detection of HbA1c. The assay procedure included immunoreactions with Fc-IgG and HbA1c, separation of immunocomplexes by boronate affinity, and electrochemical detection of Fc-IgG-HbA1c immunocomplexes. The immunoreaction mixtures were injected onto a boronate-affinity column. HbA1c-antibody complexes were then trapped onto the column by the affinity of HbA1c to boronic acid. Subsequently, elution buffer containing sorbitol was applied to elute HbA1c-antibody complexes and a current was detected by applying 600 mV versus Ag/AgCl. The elution signal was an estimation of the HbA1c amount. A linear correlation between the increase of current and HbA1c concentration was obtained up to an HbA1c concentration of 500 microg/ml. The HbA1c flow immunoassay was successfully achieved using hemolysates. This electrochemical flow immunoassay system enabled us to construct a novel point-of-care testing device for the monitoring of glycated proteins including HbA1c.     

Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes.

Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones, improving glycemic control in subjects with type 2 diabetes. This twelve-week randomized, double-masked, placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor, vildagliptin (25 mg, bid, n=70) VS. placebo (bid, n=28) in previously diet-treated subjects with type 2 diabetes. Standardized meal tests were performed at baseline and endpoint. The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 +/- 0.2 % (p=0.0012) for the whole cohort (baseline 8.0 %) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 %. Fasting glucose and mean prandial glucose were reduced by 1.1 +/- 0.4 (p=0.0043) and 1.9 +/- 0.5 mmol/l (p <0.0001), respectively. The between-group differences in corrected insulin response at peak glucose and mean prandial C-peptide were + 0.06 +/- 0.02 (p=0.0258) and + 0.10 +/- 0.03 nmol/l (p=0.0031), respectively. Vildagliptin had no effect on fasting lipid levels or body weight. The incidence of adverse events was similar in subjects receiving placebo (71.4 %) and vildagliptin (55.7 %). CONCLUSION: monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes. Concomitant improvements in beta-cell function were also observed. Subjects with higher baseline HbA1c levels showed greater response.     

An Integrated Tiered Service Delivery Model (ITSDM) Based on Local CD4 Testing Demands Can Improve Turn-Around Times and Save Costs whilst Ensuring Accessible and Scalable CD4 Services across a National Programme

Background

The South African National Health Laboratory Service (NHLS) responded to HIV treatment initiatives with two-tiered CD4 laboratory services in 2004. Increasing programmatic burden, as more patients access anti-retroviral therapy (ART), has demanded extending CD4 services to meet increasing clinical needs. The aim of this study was to review existing services and develop a service-model that integrated laboratory-based and point-of-care testing (POCT), to extend national coverage, improve local turn-around/(TAT) and contain programmatic costs.

Methods

NHLS Corporate Data Warehouse CD4 data, from 60–70 laboratories and 4756 referring health facilities was reviewed for referral laboratory workload, respective referring facility volumes and related TAT, from 2009–2012.

Results

An integrated tiered service delivery model (ITSDM) is proposed. Tier-1/POCT delivers CD4 testing at single health-clinics providing ART in hard-to-reach areas (<5 samples/day). Laboratory-based testing is extended with Tier-2/POC-Hubs (processing ≤30–40 CD4 samples/day), consolidating POCT across 8–10 health-clinics with other HIV-related testing and Tier-3/‘community’ laboratories, serving ≤40 health-clinics, processing ≤150 samples/day. Existing Tier-4/‘regional’ laboratories serve ≤100 facilities and process <350 samples/day; Tier-5 are high-volume ‘metro’/centralized laboratories (>350–1500 tests/day, serving ≥200 health-clinics). Tier-6 provides national support for standardisation, harmonization and quality across the organization.

Conclusion

The ITSDM offers improved local TAT by extending CD4 services into rural/remote areas with new Tier-3 or Tier-2/POC-Hub services installed in existing community laboratories, most with developed infrastructure. The advantage of lower laboratory CD4 costs and use of existing infrastructure enables subsidization of delivery of more expensive POC services, into hard-to-reach districts without reasonable access to a local CD4 laboratory. Full ITSDM implementation across 5 service tiers (as opposed to widespread implementation of POC testing to extend service) can facilitate sustainable ‘full service coverage’ across South Africa, and save>than R125 million in HIV/AIDS programmatic costs. ITSDM hierarchical parental-support also assures laboratory/POC management, equipment maintenance, quality control and on-going training between tiers.     

Paper-based point-of-care test with xeno nucleic acid probes

Bridging the unmet need of efficient point-of-care testing (POCT) in biomedical engineering research and practice with the emerging development in artificial synthetic xeno nucleic acids (XNAs), this review summarized the recent development in paper-based POCT using XNAs as sensing probes. Alongside the signal transducing mode and immobilization methods of XNA probes, a detailed evaluation of probe performance was disclosed. With these new aspects, both researchers in synthetic chemistry / biomedical engineering and physicians in clinical practice could gain new insights in designing, manufacturing and choosing suitable reagents and techniques for POCT.     

Effects of lifestyle modifications on patients with type 2 diabetes: the Japan Diabetes Complications Study (JDCS) study design, baseline analysis and three year-interim report.

BACKGROUND: Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes. OBJECTIVE: The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results. DESIGN: The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care. PATIENTS: The study enrolled 2 205 patients with previously diagnosed type 2 diabetes. INTERVENTION: The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer. MEASUREMENTS: Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year. RESULTS: Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available. CONCLUSIONS: The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention.