A randomised, controlled trial of self-monitoring of blood glucose in patients with type 2 diabetes receiving conventional insulin treatment.

AIMS/HYPOTHESIS: We evaluated whether self-monitoring of blood glucose (SMBG) leads to better glycaemic control (HbA(1c)) in patients with type 2 diabetes on conventional insulin regimens. METHODS: Patients with type 2 diabetes on a conventional insulin regimen (basal or premixed insulin with or without additional oral glucose-lowering agents) were recruited at study centres led by members of the German Diabetes Association. In a randomised, prospective, open 2 × 2 factorial design, the once-weekly performance of four-point glucose profiles (SMBG +; n = 151 patients) was compared with no SMBG (SMBG -; n = 149), and the measuring and transmitting of HbA1c results to the study centres (HbA(1c) +; n = 158, of these 82 SMBG - and 76 SMBG +) was compared with HbA1c measurement without disclosure of results (HbA(1c) -; n = 142, of these 67 SMBG - and 75 SMBG +). Randomised allocation was carried out by a central office, using sequentially numbered, sealed envelopes. The primary endpoint was the reduction of HbA(1c) compared with baseline after 12 months. Secondary analyses were of therapy intensification in response to higher blood or urinary glucose or HbA(1c). Participants and caregivers were not blinded as to the allocation of interventions, whereas the laboratory determining HbA(1c) remained blinded. RESULTS: Patient characteristics were balanced across groups. A total of 56 patients dropped out. In completers, HbA(1c) was reduced in the SMBG + group from 7.3% to 7.0%, i.e. by 0.3% (0.1%, 0.5%) vs SMBG - from 7.3% to 7.0% and 0.3% (0.2%, 0.5%), respectively, the difference being 0.0% (-0.2%, 0.2%) (p = 0.93). The disclosure of HbA(1c) results had no significant influence, with a difference of 0.1% (-0.1%, 0.4%) (p = 0.28). Values above are mean (95% CI). The ORs for therapy intensification significantly rose as the following increased: proportions of urine samples testing positive for glucose, HbA1c concentrations, and fasting or postprandial glucose concentrations. No important adverse events were associated with the interventions. CONCLUSIONS/INTERPRETATION: SMBG profiles once weekly or the disclosure of HbA(1c) results did not improve glycaemic control in patients with type 2 diabetes on conventional insulin treatment, although indicators of hyperglycaemia increased the likelihood of therapy intensification. Greater intensification may be necessary to impact on glycaemic control. TRIAL REGISTRATION: www.clinicaltrials.gov (registration code NCT00688363) FUNDING: Deutsche Diabetes-Gesellschaft, Deutsche Diabetes-Stiftung, Bayer Vital GmbH.

L-Arginine and SDMA Serum Concentrations Are Associated with Subclinical Atherosclerosis in the Study of Health in Pomerania (SHIP).

OBJECTIVE: Even though ˪-arginine (ARG) derivatives can predict cardiovascular mortality, their role as atherosclerotic biomarkers is unclear. We tested the hypothesis if asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and the sum of both (DMA) are positively, while ARG and ARG/ADMA ratio are inversely associated with carotid intima-media thickness (cIMT) and atherosclerotic plaque in the carotid artery. APPROACH AND RESULTS: Cross-sectional data of 1999 subjects (age: 45-81 years; 48.2% ♀) from the population-based Study of Health in Pomerania (SHIP-0) was used. Analysis of variance and logistic regression models were calculated and all adjusted models were corrected for sex, age, smoking status, waist-to-hip ratio and estimated glomerular filtration rate. Increased cIMT (>75th age-sex specific percentile) was found in 517 subjects (25.7%), while atherosclerotic plaque was detected in 1413 subjects (70.4%). SDMA tertiles were significantly positively associated with larger cIMT among subjects with high SDMA levels [>66th: 0.82 (95%-CI 0.80; 0.85) mm]. High SDMA levels were related to a higher odds ratio (OR) of increased cIMT [OR 1.39 (95%-CI 1.08; 1.79)]. Furthermore, ARG was positively associated with atherosclerotic plaques [OR 1.41 (95%-CI 1.07; 1.85)]. No relation was found for ADMA and atherosclerosis. CONCLUSIONS: In conclusion, the hypothesis of a positive association between SDMA with an increased cIMT was confirmed. Unexpectedly, ARG was positively related to atherosclerotic plaque. In view of these inconsistent findings, the impact of ARG derivatives as atherosclerotic biomarkers deserves further research.

Serum testosterone levels in males are not associated with entrepreneurial behavior in two independent observational studies.

Previous research has suggested a positive association between testosterone (T) and entrepreneurial behavior in males. However, this evidence was found in a study with a small sample size and has not been replicated. In the present study, we aimed to verify this association using two large, independent, population-based samples of males. We tested the association of T with entrepreneurial behavior, operationalized as self-employment, using data from the Rotterdam Study (N=587) and the Study of Health in Pomerania (N=1697). Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured in the serum. Free testosterone (FT), non-SHBG-bound T (non-SHBG-T), and the TT/SHBG ratio were calculated and used as measures of bioactive serum T, in addition to TT adjusted for SHBG. Using logistic regression models, we found no significant associations between any of the serum T measures and self-employment in either of the samples. To our knowledge, this is the first large-scale study on the relationship between serum T and entrepreneurial behavior.

Hemofiltration of recombinant hirudin by different hemodialyzer membranes: implications for clinical use.

Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor that is used particularly for treatment of immune-mediated heparin-induced thrombocytopenia. Because hirudin is almost exclusively eliminated by the kidneys, its half-life is markedly prolonged in patients with severe renal insufficiency. Therefore, these patients are at risk for bleeding, particularly because no antidote is available. To use hirudin safely in patients who are on renal replacement therapy, knowledge of hirudin-sieving characteristics of different hemodialyzers is required. Data on this issue are sparse and in part contradictory. Eight different conventional low-flux and high-flux hemodialyzers were tested in an in vitro circuit with ultrafiltrate reinfusion. In each experiment, lepirudin concentration was repetitively measured during 3 h in the prefilter, the postfilter, and the filtration line using a chromogenic assay. On the basis of these data, sieving coefficients were calculated. All high-flux hemodialyzers tested allowed filtration of hirudin yet with marked differences in steady-state sieving (sieving coefficients in whole blood: polysulfone [PS] 0.97 +/- 0.03; polymethylmethacrylate [PMMA] 0.75 +/- 0.02; polyarylethersulfone 0.73 +/- 0.02; polyamide 0.49 +/- 0.02). None of the low-flux hemodialyzer membranes tested (cuprophane, hemophane, PS, and PMMA) showed significant hirudin filtration. Owing to marked differences in hirudin-sieving characteristics, choice of the appropriate hemodialyzer membrane is an important determinant of bleeding risk in dialysis-dependent patients who are treated with hirudin. In case of overdosage or bleeding complications, hemofiltration via PS membranes is recommended to reduce plasma hirudin concentration. Hirudin dosage should be adapted not only to the clinical situation but also to the hirudin-sieving characteristics of the assigned dialyzer.