Sex-specific-differences in cardiometabolic risk in type 1 diabetes: a cross-sectional study.

BACKGROUND: Little is known about the impact of sex-specific differences in the management of type 1 diabetes (T1DM). Thus, we evaluated the influence of gender on risk factors, complications, clinical care and adherence in patients with T1DM. METHODS: In a cross-sectional study, sex-specific disparities in glycaemic control, cardiovascular risk factors, diabetic complications, concomitant medication use and adherence to treatment recommendations were evaluated in 225 consecutive patients (45.3% women) who were comparable with respect to age, diabetes duration, and body mass index. RESULTS: Although women with T1DM had a higher total cholesterol than men, triglycerides were higher in obese men and males with HbA1c>7% than in their female counterparts. No sex differences were observed in glycaemic control and in micro- or macrovascular complications. However, the subgroup analysis showed that nephropathy was more common in obese men, hyperlipidaemic women and all hypertensive patients, whereas peripheral neuropathy was more common in hyperlipidaemic women. Retinopathy was found more frequently in women with HbA1c>7%, obese men and in both sexes with a long duration of diabetes. The multivariate analysis revealed that microvascular complications were associated with the duration of disease and BMI in both sexes and with hyperlipidaemia in males. The overall adherence to interventions according to the guidelines was higher in men than in women. This adherence was concerned particularly with co-medication in patients diagnosed with hypertension, aspirin prescription in elderly patients and the achievement of target lipid levels following the prescription of statins. CONCLUSIONS: Our data showed sex differences in lipids and overweight in patients with T1DM. Although glycaemic control and the frequency of diabetic complications were comparable between the sexes, the overall adherence to guidelines, particularly with respect to the prescription of statins and aspirin, was lower in women than in men.

Clinical characteristics, modalities and complications of diabetic patients with migration background at a Central European University Clinic.

The objective of the present study was to assess (i) the effects of immigration on the outcome of 200 consecutive singleton pregnancies in women with overt diabetes as well as (ii) gender-specific differences in cardiovascular risk factor profile and the achievement of therapeutic targets in type 2 diabetic subjects with migration background (n = 50). In pregnant subjects, baseline characteristics at admission, pregnancy outcome and the rate of obstetrical complications were similar in immigrant and non-immigrant women. Type 2 diabetes and also preconceptionally undiagnosed diabetes were significantly more frequent in women with migration background. Following delivery, immigrants presented with a worse metabolic profile, including higher triglyceride and nonHDL levels, than the indigenous population. Furthermore, within diabetic subjects with a migration background, non-pregnant women feature a more adverse cardiovascular risk factor profile than men. However, no gender-specific differences in the total adherence to clinical recommendations according to clinical recommendations have been found.

Evaluation of educational needs in patients with diabetes mellitus in respect of medication use in Austria.

BACKGROUND: Effective control of diabetes mellitus type 1 (DM1) and type 2 (DM2) can reduce the development and progression of diabetic complications. Therefore, patient education should be considered as an integral part of diabetes management. OBJECTIVE: The aim of the study was to assess DM patients' perception of knowledge for their medication and attitude towards self-management and pharmacist's role. SETTING: The study was conducted at the diabetes out-patient clinic at the Vienna General Hospital (AKH), Division of Endocrinology and Metabolism, Department of Internal Medicine III, Austria. METHOD: The study was a cross sectional survey using patient data from a validated patient questionnaire and medical records. Medical records were evaluated by applying a medication assessment tool. MAIN OUTCOME MEASURE: To assess the quality of diabetes self management the following outcome measures are considered: HbA1c levels, pre- and post-prandial blood glucose levels, prevention of acute episodes of hypo- and hyperglycaemia, reduction of macrovascular risk factors, short term quality of life, adverse effects and treatment tolerance. RESULTS: The present study comprised 225 patients with DM1 and 201 patients with DM2, respectively. In comparison to DM2 patients, cardio- and cerebrovascular diseases were diagnosed very rarely in patients with DM1. The risk for these diseases was higher in patients with other factors of the metabolic syndrome, in addition. Overall, 118 of these patients participated in the questionnaire. The level of positive response on diabetes self-care and knowledge with respect to medication for the prevention of diabetes complications, glycaemic control, and treatment goals in diabetes was 81.8 %. The comparison of patients' perceptions of diabetes self-care and knowledge showed differences among subgroups. Higher perceived knowledge and self-care apparently was associated with DM1. Additional findings of this study indicate that patients do not expect community pharmacists to be integrated in a multidisciplinary diabetes care team. CONCLUSION: Although the level of positive response was found to be high there is still a minority of patients whose level of comprehension appears to be insufficient. Intense pharmaceutical care including patients' education within a multidisciplinary team could contribute to improvements in those patients.

Evidence-based intravenous pain treatment with analgesic infusion regimens.

BACKGROUND AND OBJECTIVE: To survey all bedside-prepared analgesic infusions (two or more drugs within one vehicle) at a 1000-bed general hospital. To evaluate appropriate vehicles and acceptable drug combinations in analgesic infusions with regard to evidence-based therapy. DESIGN: Literature review; computer simulation of pharmacokinetics with MATLAB 6.5; evaluation of pharmacokinetic or pharmacodynamic interactions and dose regimens. MAIN OUTCOME MEASURES: Categorisation of 19 infusion combinations used for the management of pain into acceptable and questionable combinations of components in terms of quality assurance evaluation. RESULTS: Diclofenac sodium (CAS 15307-79-6), metamizole sodium (CAS 68-89-3) and tramadol hydrochloride (CAS 36282-47-0) were combined with diazepam (CAS 439-14-5), B-vitamins (CAS 67-03-8, 130-40-5, 58-56-0, 68-19-9, 98-92-0, 137-08-6), lidocaine hydrochloride (CAS 73-78-9), metoclopramide dihydrochloride (CAS 54143-57-6) and pantoprazole sodium (CAS 138786 7-1). The vehicles were Ringer, Ringer lactate, normal saline or an infusion product containing diclofenac sodium and orphenadrine citrate (CAS 4682-36-4). In 37% the vehicle used was not one recommended by the manufacturer or an incompatibility was mentioned in the product information. The combinations of diclofenac sodium or tramadol with diazepam induce a long-lasting sedative effect by diazepam and its metabolite, but only a moderate duration of analgesia. The combination of diclofenac sodium and metamizole sodium is acceptable, although, at a lower dosage of metamizole, the duration of analgesia is shortened. No or insufficient data on therapeutic plasma levels and safe dosages has been reported for lidocaine and B-vitamins. CONCLUSIONS: For all of the drug combinations in use, no interactions of clinical relevance are to be expected. In 37% of the nineteen bedside-prepared infusions, the vehicle was not suitable or incompatibilities were cited in the product information. The combinations of metamizole sodium and diclofenac sodium or tramadol in normal saline solution were in accordance with evidence-based medicine. However, changing some infusion regimens might achieve optimisation of pain treatment with respect to duration of analgesia, and the applied number of drugs could be reduced by omitting additives with little clinical effectiveness.

Sex-specific differences in metabolic control, cardiovascular risk, and interventions in patients with type 2 diabetes mellitus.

BACKGROUND: Sex-specific differences appear particularly relevant in the management of type 2 diabetes mellitus (T2DM), with women experiencing greater increases in cardiovascular morbidity and mortality than do men. OBJECTIVE: The aim of this article was to investigate the influence of biological sex on clinical care and microvascular and macrovascular complications in patients with T2DM in a Central European university diabetes clinic. METHODS: In a cross-sectional study, sex-specific disparities in metabolic control, cardiovascular risk factors, and diabetic complications, as well as concomitant medication use and adherence to treatment recommendations, were evaluated in 350 consecutive patients who were comparable for age, diabetes duration, and body mass index. Study inclusion criteria included age ≤75 years, T2DM, a documented history of presence or absence of coronary heart disease (CHD), and informed consent. Patients were followed in the diabetes outpatient clinic between November 2007 and March 2008. RESULTS: Two hundred and one patients with T2DM met inclusion criteria (93 [46.3%] women, 108 [53.7%] men). Women with T2DM had higher mean (SE) systolic blood pressure (155.4 [22.5] vs 141.0 [19.8] mm Hg for men; P < 0.001) and total cholesterol (TC) (5.28 [1.34] vs 4.86 [1.29] mmol/L for men; P < 0.05), but a lower TC:HDL-C ratio (4.1 [1.19] vs 4.5 [1.2] for men; P < 0.05). Slightly more men (32.4%) than women (26.9%) reached the therapeutic goal of <7.0% for glycosylated hemoglobin. Women with shorter diabetes duration (<10 years) received oral antihyperglycemic therapy less frequently (P < 0.05). Women with longer disease duration had hypertension more frequently than did their male counterparts (100% vs 86.0%, respectively; P < 0.01). Despite a similar rate of CHD, men were twice as likely as women to have had coronary interventions (percutaneous transluminal coronary angioplasty/coronary artery bypass graft, 25.0% vs 12.9%, respectively; P < 0.05). Women with CHD also had a higher rate of cerebral ischemia than did men (27.6% vs 5.4%, respectively; P < 0.05) and received aspirin less frequently for secondary prevention (P < 0.001). Men had greater overall adherence to diabetes and cardiovascular risk guidelines than did women (66.4% vs 58.9%, respectively; P < 0.01). CONCLUSIONS: In this study of diabetes clinic outpatients, women with T2DM had a worse cardiovascular risk profile and achieved therapeutic goals less frequently than did men. Treatment strategies should be improved in both sexes, but women with diabetes may be in need of more aggressive treatment, especially when cardiovascular disease is present.

Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells.

Worldwide, multiple Fusarium mycotoxins occur as contaminants of cereals with important impacts on human and animal health. The aim of this study was to investigate the effects of the widespread Fusarium secondary metabolite enniatin (ENN), a cyclic hexadepsipeptide, on human cell growth and survival. While short-term exposure (up to 8 h) to ENN at nanomolar concentrations slightly but significantly stimulated cell proliferation, it showed profound apoptosis-inducing effects especially against various human cancer cell types at low micromolar concentrations (already after 24 h of treatment). Several cellular changes indicative for programmed cell death such as cell shrinkage, chromatin condensation, DNA fragmentation, and apoptotic body formation were observed. Correspondingly, the cleavage of poly(ADP-ribosyl)polymerase and the activation of multiple caspases accompanied a distinct loss of mitochondrial membrane potential. To investigate the impact of apoptosis- and cell cycle-regulating proteins on ENN activity, HCT116 cells with homozygously disrupted p53, p21, or bax genes were analyzed. In vitality assays, no significant influences of these proteins on the anticancer activity of ENN were detectable. In contrast, 3H-thymidine incorporation revealed a significantly more efficient block of DNA synthesis in p53 wild-type as compared to knock-out cells. Accordingly, fluorescence-activated cell sorting analysis demonstrated a stronger ENN-induced cell cycle arrest in the G0/G1 phase. Profound ENN-mediated induction of p53 and the p53-downstream cell cycle inhibitor p21 were detectable in p53 wild-type cells by Western blotting. P53-independent p21 induction was also detectable at higher ENN concentrations in p53 (-/-) cells. In contrast, bax activation by ENN was independent of the cellular p53 status. In summary, our results suggest that short-term exposure to very low ENN concentrations, for example, via food intake, might have tumor-promoting functions based on growth stimulation. In contrast, elevated ENN concentrations exert profound p53-dependent cytostatic and p53-independent cytotoxic activities especially against human cancer cells, suggesting a potential quality of ENN as an anticancer drug.