Addressing schemes of self-monitoring of blood glucose in type 2 diabetes: a European perspective and expert recommendation

Self-monitoring of blood glucose (SMBG) in type 2 diabetes has increasingly been shown to display beneficial effects on glycemic control. SMBG is not only associated with a reduction of hemoglobin A1c but has also been demonstrated to increase patients' awareness of the disease. SMBG has also the potential to visualize and predict hypoglycemic episodes. International guidelines by the International Diabetes Federation, the European Society of Cardiology, and the European Association for the Study of Diabetes and also the International Society for Pediatric and Adolescent Diabetes emphasize that SMBG is an integral part of self-management. More recently, two European consensus documents have been published to give recommendations for frequency and timing of SMBG also for various clinical scenarios. Recently, a European expert panel was held to further facilitate and enhance standardized approaches to SMBG. The aim was to present simple, clinically meaningful, and standardized SMBG strategies for type 2 diabetes. The panel recommended a less intensive and an intensive scheme for SMBG across the type 2 diabetes continuum. The length and frequency of SMBG performance depend on the clinical circumstances and the quality of glycemic control. The expert panel also recommended further evaluation of various schemes for SMBG in type 2 diabetes in clinical studies.

[What you always wanted to know about HbA1c]

Irreversible, nonenzymatic glycation of the haemoglobin A beta chain leads to the formation of haemoglobin A1c (HbA1c), a stable minor haemoglobin component with enhanced electrophoretic mobility. The rate of formation of HbA1c is directly proportional to the ambient glucose concentration. HbA1c is commonly used to assess long-term blood glucose control in patients with diabetes mellitus, because the HbA1c value has been shown to predict the risk for the development of many of the chronic complications in diabetes. There are currently four principal glycohaemoglobin assay techniques (ion-exchange chromatography, electrophoresis, affinity chromatography and immunoassays) and over 20 methods that measure different glycated products. The ranges indicating good and poor glycaemic control can vary markedly between different assays. At the moment values differ between methodologies and even between different laboratories using the same methodology. Optimal use of HbA1c testing requires standardisation. There is progress towards international standardisation and improved precision of HbA1c which will lead to all assays reporting results in a standardised way. Clinicians ordering HbA1c testing for their patients should be aware of the type of assay method used, the reference interval, potential assay interferences (e.g. haemoglobinopathies, chronic alcohol ingestion, carbamylation products in uraemia) and assay performance. And they should know that a variety of factors have been shown to directly influence HbA1c values, e.g. iron deficiency anaemia, chronic renal failure and shortened red blood cell life span.

Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a stable isotope study

Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P < 0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P < 0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P < 0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P < 0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P < 0.01). The total cholesterol concentration (P < 0.02), the low density lipoprotein cholesterol concentration (P < 0.02), and the VLDL cholesterol/VLDL apoB ratio (P < 0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P < 0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P < 0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.

Notification of abnormal lab test results in an electronic medical record: do any safety concerns remain?

BACKGROUND: Follow-up of abnormal outpatient laboratory test results is a major patient safety concern. Electronic medical records can potentially address this concern through automated notification. We examined whether automated notifications of abnormal laboratory results (alerts) in an integrated electronic medical record resulted in timely follow-up actions. METHODS: We studied 4 alerts: hemoglobin A1c > or =15%, positive hepatitis C antibody, prostate-specific antigen > or =15 ng/mL, and thyroid-stimulating hormone > or =15 mIU/L. An alert tracking system determined whether the alert was acknowledged (ie, provider clicked on and opened the message) within 2 weeks of transmission; acknowledged alerts were considered read. Within 30 days of result transmission, record review and provider contact determined follow-up actions (eg, patient contact, treatment). Multivariable logistic regression models analyzed predictors for lack of timely follow-up. RESULTS: Between May and December 2008, 78,158 tests (hemoglobin A1c, hepatitis C antibody, thyroid-stimulating hormone, and prostate-specific antigen) were performed, of which 1163 (1.48%) were transmitted as alerts; 10.2% of these (119/1163) were unacknowledged. Timely follow-up was lacking in 79 (6.8%), and was statistically not different for acknowledged and unacknowledged alerts (6.4% vs 10.1%; P =.13). Of 1163 alerts, 202 (17.4%) arose from unnecessarily ordered (redundant) tests. Alerts for a new versus known diagnosis were more likely to lack timely follow-up (odds ratio 7.35; 95% confidence interval, 4.16-12.97), whereas alerts related to redundant tests were less likely to lack timely follow-up (odds ratio 0.24; 95% confidence interval, 0.07-0.84). CONCLUSIONS: Safety concerns related to timely patient follow-up remain despite automated notification of non-life-threatening abnormal laboratory results in the outpatient setting.

Rapid effects of 1alpha,25-dihydroxyvitamin D3 on osteoblasts: Studies of membrane transducers that affect calcium signals

1,25-dihydroxyvitamin D3 [1,25(OH)2D 3] exerts pleiotropic effects on osteoblasts via both long-term nuclear receptor-mediated and rapid membrane-initiated pathways during bone remodeling and mineral homeostasis. This study explored the membrane transducers that mediate rapid effects of 1,25(OH)2D3 on osteoblasts, including sphingomyelinase (SMase) and L-type voltage sensitive calcium channels (VSCCs). ^ It was previously demonstrated that 1,25(OH)2D3 stimulates transmembrane influx of Ca2+ through VSCCs in ROS 17/2.8 osteoblasts, however the molecular identity of 1,25(OH)2D 3-regulated VSCC has not been known. In this study, on the basis of in vitro tests of three unique ribozymes specifically cleaving a1C mRNA, I transfected ROS 17/2.8 cells with vectors coding recombinant ribozyme modified with U1 snRNA structure, and successfully selected stable clonal cells in which the expression of a1C was strikingly reduced. Ca2+ influx studies in these cells compared to control transfectants showed selective attenuation of depolarization- and 1,25(OH)2D3-regulated Ca2+ responses. These results allow us to conclude that the cardiac ( a1C ) subtype of the L-type VSCC is the major membrane transducer of Ca 2+ influx in osteoblasts. ^ I also demonstrated that 1,25(OH)2D3 induces a rapid hydrolysis of membrane sphingomyelin (SM) in ROS 17/2.8 cells, with the concomitant generation of ceramide, detectable at 15 minute, and maximal at 1 hour after addition. Sphingosine, sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPC), downstream products of SM hydrolysis, but not ceramide, elicit Ca 2+ release from intracellular stores. Considering ceramide, sphingosine, and SPP as second messengers modulating intracellular kinases or phosphatases, these findings implicate sphingolipid-signaling pathways in transducing rapid effects of 1,25(OH)2D3 on osteoblasts. In structure/function analyses of sphingolipid signaling, it was observed that psychosine elicits Ca2+ release from intracellular stores. This challenges the dogma that sphingosine phosphorylation permits mobilization of Ca2+ , because psychosine is a sphingosine analog galactosylated at 1-carbon, preventing phosphorylation at that site. Psychosine is the pathological metabolite found in patients with Krabbe's disease, suggesting that psychosine disrupts the physiological sphingolipid signaling by chronic release of Ca2+ from intracellular stores. ^ Slower SM turnover than Ca2+ influx through VSCCs in response to 1,25(OH)2D3 demonstrates ceramide does not mediate the 1,25(OH)2D3-induced Ca2+ signaling, a conclusion endorsed further by the failure of ceramide to induce Ca 2+ signaling. ^

Evolving biomarkers improve prediction of long-term mortality in patients with stable coronary artery disease: the BIO-VILCAD score.

OBJECTIVE Algorithms to predict the future long-term risk of patients with stable coronary artery disease (CAD) are rare. The VIenna and Ludwigshafen CAD (VILCAD) risk score was one of the first scores specifically tailored for this clinically important patient population. The aim of this study was to refine risk prediction in stable CAD creating a new prediction model encompassing various pathophysiological pathways. Therefore, we assessed the predictive power of 135 novel biomarkers for long-term mortality in patients with stable CAD. DESIGN, SETTING AND SUBJECTS We included 1275 patients with stable CAD from the LUdwigshafen RIsk and Cardiovascular health study with a median follow-up of 9.8 years to investigate whether the predictive power of the VILCAD score could be improved by the addition of novel biomarkers. Additional biomarkers were selected in a bootstrapping procedure based on Cox regression to determine the most informative predictors of mortality. RESULTS The final multivariable model encompassed nine clinical and biochemical markers: age, sex, left ventricular ejection fraction (LVEF), heart rate, N-terminal pro-brain natriuretic peptide, cystatin C, renin, 25OH-vitamin D3 and haemoglobin A1c. The extended VILCAD biomarker score achieved a significantly improved C-statistic (0.78 vs. 0.73; P = 0.035) and net reclassification index (14.9%; P < 0.001) compared to the original VILCAD score. Omitting LVEF, which might not be readily measureable in clinical practice, slightly reduced the accuracy of the new BIO-VILCAD score but still significantly improved risk classification (net reclassification improvement 12.5%; P < 0.001). CONCLUSION The VILCAD biomarker score based on routine parameters complemented by novel biomarkers outperforms previous risk algorithms and allows more accurate classification of patients with stable CAD, enabling physicians to choose more personalized treatment regimens for their patients.

Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of incident gout: a population-based case-control study

OBJECTIVE The aim of this study was to explore the risk of incident gout in patients with type 2 diabetes mellitus (T2DM) in association with diabetes duration, diabetes severity and antidiabetic drug treatment. METHODS We conducted a case-control study in patients with T2DM using the UK-based Clinical Practice Research Datalink (CPRD). We identified case patients aged ≥18 years with an incident diagnosis of gout between 1990 and 2012. We matched to each case patient one gout-free control patient. We used conditional logistic regression analysis to calculate adjusted ORs (adj. ORs) with 95% CIs and adjusted our analyses for important potential confounders. RESULTS The study encompassed 7536 T2DM cases with a first-time diagnosis of gout. Compared to a diabetes duration <1 year, prolonged diabetes duration (1-3, 3-6, 7-9 and ≥10 years) was associated with decreased adj. ORs of 0.91 (95% CI 0.79 to 1.04), 0.76 (95% CI 0.67 to 0.86), 0.70 (95% CI 0.61 to 0.86), and 0.58 (95% CI 0.51 to 0.66), respectively. Compared to a reference A1C level of <7%, the risk estimates of increasing A1C levels (7.0-7.9, 8.0-8.9 and ≥9%) steadily decreased with adj. ORs of 0.79 (95% CI 0.72 to 0.86), 0.63 (95% CI 0.55 to 0.72), and 0.46 (95% CI 0.40 to 0.53), respectively. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. CONCLUSIONS Increased A1C levels, but not use of antidiabetic drugs, was associated with a decreased risk of incident gout among patients with T2DM.

Comparison of telomere length in black and white teachers from South Africa: the sympathetic activity and ambulatory blood pressure in Africans study

OBJECTIVE Telomere length is a marker of biological aging that has been linked to cardiovascular disease risk. The black South African population is witnessing a tremendous increase in the prevalence of cardiovascular disease, part of which might be explained through urbanization. We compared telomere length between black South Africans and white South Africans and examined which biological and psychosocial variables played a role in ethnic difference in telomere length. METHODS We measured leukocyte telomere length in 161 black South African teachers and 180 white South African teachers aged 23 to 66 years without a history of atherothrombotic vascular disease. Age, sex, years having lived in the area, human immunodeficiency virus (HIV) infection, hypertension, body mass index, dyslipidemia, hemoglobin A1c, C-reactive protein, smoking, physical activity, alcohol abuse, depressive symptoms, psychological distress, and work stress were considered as covariates. RESULTS Black participants had shorter (median, interquartile range) relative telomere length (0.79, 0.70-0.95) than did white participants (1.06, 0.87-1.21; p < .001), and this difference changed very little after adjusting for covariates. In fully adjusted models, age (p < .001), male sex (p = .011), and HIV positive status (p = .023) were associated with shorter telomere length. Ethnicity did not significantly interact with any covariates in determining telomere length, including psychosocial characteristics. CONCLUSIONS Black South Africans showed markedly shorter telomeres than did white South African counterparts. Age, male sex, and HIV status were associated with shorter telomere length. No interactions between ethnicity and biomedical or psychosocial factors were found. Ethnic difference in telomere length might primarily be explained by genetic factors.

The cystatin C/creatinine ratio, a marker of glomerular filtration quality: associated factors, reference intervals, and prediction of morbidity and mortality in healthy seniors.

The ratio of cystatin C (cysC) to creatinine (crea) is regarded as a marker of glomerular filtration quality associated with cardiovascular morbidities. We sought to determine reference intervals for serum cysC-crea ratio in seniors. Furthermore, we sought to determine whether other low-molecular weight molecules exhibit a similar behavior in individuals with altered glomerular filtration quality. Finally, we investigated associations with adverse outcomes. A total of 1382 subjectively healthy Swiss volunteers aged 60 years or older were enrolled in the study. Reference intervals were calculated according to Clinical & Laboratory Standards Institute (CLSI) guideline EP28-A3c. After a baseline exam, a 4-year follow-up survey recorded information about overall morbidity and mortality. The cysC-crea ratio (mean 0.0124 ± 0.0026 mg/μmol) was significantly higher in women and increased progressively with age. Other associated factors were hemoglobin A1c, mean arterial pressure, and C-reactive protein (P < 0.05 for all). Participants exhibiting shrunken pore syndrome had significantly higher ratios of 3.5-66.5 kDa molecules (brain natriuretic peptide, parathyroid hormone, β2-microglobulin, cystatin C, retinol-binding protein, thyroid-stimulating hormone, α1-acid glycoprotein, lipase, amylase, prealbumin, and albumin) and creatinine. There was no such difference in the ratios of very low-molecular weight molecules (urea, uric acid) to creatinine or in the ratios of molecules larger than 66.5 kDa (transferrin, haptoglobin) to creatinine. The cysC-crea ratio was significantly predictive of mortality and subjective overall morbidity at follow-up in logistic regression models adjusting for several factors. The cysC-crea ratio exhibits age- and sex-specific reference intervals in seniors. In conclusion, the cysC-crea ratio may indicate the relative retention of biologically active low-molecular weight compounds and can independently predict the risk for overall mortality and morbidity in the elderly.

Impaired glucose metabolism and type 2 diabetes in apparently healthy senior citizens

STUDY PRINCIPLE To estimate the prevalence of unknown impaired glucose metabolism, also referred to as prediabetes (PreD), and unknown type 2 diabetes mellitus (T2DM) among subjectively healthy Swiss senior citizens. The fasting plasma glucose (FPG) and glycated haemoglobin A1c (HbA1c) levels were used for screening. A total of 1 362 subjects were included (613 men and 749 women; age range 60-99 years). Subjects with known T2DM were excluded. METHODS The FPG was processed immediately for analysis under standardised preanalytical conditions in a cross-sectional cohort study; plasma glucose levels were measured by means of the hexokinase procedure, and HbA1c was measured chromatographically and classified using the current American Diabetes Association (ADA) criteria. RESULTS The crude prevalence of individuals unaware of having prediabetic FPG or HbA1c levels, was 64.5% (n = 878). Analogously, unknown T2DM was found in 8.4% (n = 114) On the basis of HbA1c criteria alone, significantly more subjects with unknown fasting glucose impairment and laboratory T2DM could be identified than with the FPG. The prevalence of PreD as well as of T2DM increased with age. The mean HOMA indices (homeostasis model assessment) for the different age groups, between 2.12 and 2.59, are consistent with clinically hidden disease and are in agreement with the largely orderly Body Mass Indices found in the normal range. CONCLUSIONS Laboratory evidence of impaired glucose metabolism and, to a lesser extent, unknown T2DM, has a high prevalence among subjectively healthy older Swiss individuals. Laboratory identification of people with unknown out-of-range glucose values and overt diabetic hyperglycaemia might improve the prognosis by delaying the emergence of overt disease.

Outcomes and cost effectiveness of treating type 2 diabetes with a nurse case manager following treatment algorithms versus primary care physicians

Background. Diabetes places a significant burden on the health care system. Reduction in blood glucose levels (HbA1c) reduces the risk of complications; however, little is known about the impact of disease management programs on medical costs for patients with diabetes. In 2001, economic costs associated with diabetes totaled $100 billion, and indirect costs totaled $54 billion. ^ Objective. To compare outcomes of nurse case management by treatment algorithms with conventional primary care for glycemic control and cardiovascular risk factors in type 2 diabetic patients in a low-income Mexican American community-based setting, and to compare the cost effectiveness of the two programs. Patient compliance was also assessed. ^ Research design and methods. An observational group-comparison to evaluate a treatment intervention for type 2 diabetes management was implemented at three out-patient health facilities in San Antonio, Texas. All eligible type 2 diabetic patients attending the clinics during 1994–1996 became part of the study. Data were obtained from the study database, medical records, hospital accounting, and pharmacy cost lists, and entered into a computerized database. Three groups were compared: a Community Clinic Nurse Case Manager (CC-TA) following treatment algorithms, a University Clinic Nurse Case Manager (UC-TA) following treatment algorithms, and Primary Care Physicians (PCP) following conventional care practices at a Family Practice Clinic. The algorithms provided a disease management model specifically for hyperglycemia, dyslipidemia, hypertension, and microalbuminuria that progressively moved the patient toward ideal goals through adjustments in medication, self-monitoring of blood glucose, meal planning, and reinforcement of diet and exercise. Cost effectiveness of hemoglobin AI, final endpoints was compared. ^ Results. There were 358 patients analyzed: 106 patients in CC-TA, 170 patients in UC-TA, and 82 patients in PCP groups. Change in hemoglobin A1c (HbA1c) was the primary outcome measured. HbA1c results were presented at baseline, 6 and 12 months for CC-TA (10.4%, 7.1%, 7.3%), UC-TA (10.5%, 7.1%, 7.2%), and PCP (10.0%, 8.5%, 8.7%). Mean patient compliance was 81%. Levels of cost effectiveness were significantly different between clinics. ^ Conclusion. Nurse case management with treatment algorithms significantly improved glycemic control in patients with type 2 diabetes, and was more cost effective. ^

The effectiveness of a promotora-led intervention for Mexican Americans with type 2 diabetes

Purpose. The purpose of this randomized control repeated measures trial was to determine the effectiveness of a self-management intervention led by community lay workers called promotoras on the health outcomes of Mexican Americans with type 2 diabetes living in a major city on the Texas - Mexico border. The specific aims of this study, in relation to the intervention group participants, were to: (1) decrease the glycosylated hemoglobin (A1c) blood levels at the six-month assessment, (2) increase diabetes knowledge at the three and six-month assessments, and (3) strengthen the participants' beliefs in their ability to manage diabetes at the three and six-month assessments.^ Methods. One hundred and fifty Mexican American participants were recruited at a Catholic faith-based clinic and randomized into an intervention group and a usual-care control group. Personal characteristics, acculturation and baseline A1c, diabetes knowledge and diabetes health beliefs were measured. The six-month, two-phase intervention was culturally specific and it was delivered entirely by promotoras. Phase One of the intervention consisted of sixteen hours of participative group education and bi-weekly telephone contact follow-up. Phase Two consisted of bi-weekly follow-up using inspirational faith-based health behavior change postcards. The A1c levels, diabetes knowledge and diabetes health beliefs were measured at baseline, and three and six months post-baseline. The mean changes between the groups were analyzed using analysis of covariance. ^ Results. The 80% female sample, with a mean age of 58 years, demonstrated very low: acculturation, income, education, health insurance coverage, and strong Catholicism. No significant changes were noted at the three-month assessment, but the mean change of the A1c levels (F (1, 148 = 10.28, p < .001) and the diabetes knowledge scores (F (1, 148 = 9.0, p < .002) of the intervention group improved significantly at six months, adjusting for health insurance coverage. The diabetes health belief scores decreased in both groups.^ Conclusions. This study demonstrated that an intervention led by promotoras could result in decreased A1c levels and increased diabetes knowledge in spite of the very low acculturation, educational level and insurance coverage of the intervention group participants. Clinical implications and recommendations for future research are suggested. ^

The impact of nutrition intervention on glycemic control in a pediatric type 1 diabetes mellitus population

Aim: The goal of this study was to evaluate the change in hemoglobin A1C and glycemic control after nutrition intervention among a population of type 1 diabetic pediatric patients. Methods: Data was collected from all type 1 diabetic patients who were scheduled for a consultation with the diabetes/endocrine RD from January 2006 through December 2006. Two groups were compared, those who kept their RD appointment and those who did not keep their appointment. The main outcome measure was HgbA1C. An independent samples t-test compared the two groups with respect to change in HbgA1C before and after the most recent scheduled appointment with the RD. Baseline characteristics were used as covariates and analyzed and controlled for using analysis of covariance (ANCOVA). Results: There was no difference in HgbA1c after either attending an RD appointment or not having attended an RD appointment. Those who arrived for and attended their RD appointment and those who did not arrive for and attend their RD appointment, had statistically different HgbA1C's before their scheduled appointment as well as after the RD appointment. However, the two groups were not equal at the beginning of the study period. Discussion: A study design with inclusion criteria of a specified range of HgbA1C values within which the study subjects needed to fall, would have potentially eliminated the difference between the two groups at the beginning of the study period. Conducting either another retrospective study that controlled for the initial HgbA1C value or conducting a prospective study that designated a range of HgbA1C values would be worth investigating to evaluate the impact of medical nutrition therapy intervention and the role of the RD in diabetes management. It is an interesting finding that there was a significant difference in the initial HgbA1c for those who came to the RD appointment compared to those who did not come. The fact that in this study those who did not arrive for their RD appointment had worse control of their diabetes suggests that this is a high-risk group. Targeting diabetes education toward this group of patients may prove to be beneficial. ^

Health outcomes, quality improvement and cost-effectiveness of the Community Diabetes Education (CoDE) program: Results of a randomized controlled trial

The objectives of this dissertation were to evaluate health outcomes, quality improvement measures, and the long-term cost-effectiveness and impact on diabetes-related microvascular and macrovascular complications of a community health worker-led culturally tailored diabetes education and management intervention provided to uninsured Mexican Americans in an urban faith-based clinic. A prospective, randomized controlled repeated measures design was employed to compare the intervention effects between: (1) an intervention group (n=90) that participated in the Community Diabetes Education (CoDE) program along with usual medical care; and (2) a wait-listed comparison group (n=90) that received only usual medical care. Changes in hemoglobin A1c (HbA1c) and secondary outcomes (lipid status, blood pressure and body mass index) were assessed using linear mixed-models and an intention-to-treat approach. The CoDE group experienced greater reduction in HbA1c (-1.6%, p<.001) than the control group (-.9%, p<.001) over the 12 month study period. After adjusting for group-by-time interaction, antidiabetic medication use at baseline, changes made to the antidiabetic regime over the study period, duration of diabetes and baseline HbA1c, a statistically significant intervention effect on HbA1c (-.7%, p=.02) was observed for CoDE participants. Process and outcome quality measures were evaluated using multiple mixed-effects logistic regression models. Assessment of quality indicators revealed that the CoDE intervention group was significantly more likely to have received a dilated retinal examination than the control group, and 53% achieved a HbA1c below 7% compared with 38% of control group subjects. Long-term cost-effectiveness and impact on diabetes-related health outcomes were estimated through simulation modeling using the rigorously validated Archimedes Model. Over a 20 year time horizon, CoDE participants were forecasted to have less proliferative diabetic retinopathy, fewer foot ulcers, and reduced numbers of foot amputations than control group subjects who received usual medical care. An incremental cost-effectiveness ratio of $355 per quality-adjusted life-year gained was estimated for CoDE intervention participants over the same time period. The results from the three areas of program evaluation: impact on short-term health outcomes, quantification of improvement in quality of diabetes care, and projection of long-term cost-effectiveness and impact on diabetes-related health outcomes provide evidence that a community health worker can be a valuable resource to reduce diabetes disparities for uninsured Mexican Americans. This evidence supports formal integration of community health workers as members of the diabetes care team.^

Influence of allelic prolamin variation and localities on durum wheat quality

Thirty-seven varieties of a Mediterranean durum wheat collection grown in Tunisia and Spain were analysed for their allelic composition in prolamins, as well as their protein concentration, sodium dodecyl sulphate sedimentation (SDSS) test and mixograph parameters. Genotype was a greater source of variation in all measurements than locality. Uncommon high and low molecular glutenin subunits (HMW-GS and LMW-GS) were found (V and 2? subunits at Glu-A1, 13 þ 16 at Glu-B1, 5* subunit and ax allele at Glu-A3). The rare combinations 2 þ 4þ14 þ 18 and 8 þ 9þ13 þ 16þ18 subunits at the Glu-B3 locus were found. Glu-A3ax had a positive influence on SDSS and mixograph parameters. Of all the prolamins, those that have the B-LMW-GS composition aaa (for Glu-A3, Glu-B3 and Glu-B2 loci, respectively), when associated with the Glu-A1c and Glu-B1d gave the best semolina quality. By contrast, semolina quality is poor when this same composition is associated with the Glu-A1c and Glu-B1e and even poorer when associated with the Glu-A1c and Glu-B1f. In addition, the cultivars with B-LMW-GS allelic composition aab (for Glu-A3, Glu-B3 and Glu-B2 loci, respectively), when associated with the Glu- A1c and Glu-B1d, gave high quality, whereas when associated with the Glu-A1c and Glu-B1e or with Glu- A1o and Glu-B1f, the quality was very poor.