Efficacy and safety of biphasic insulin aspart 30 combined with pioglitazone in type 2 diabetes poorly controlled on glibenclamide (glyburide) monotherapy or combination therapy: an 18-week, randomized, open-label study

BACKGROUND: Few large randomized controlled trials have assessed the value of adding insulin to an oral antidiabetic drug regimen. OBJECTIVE: This trial compared the efficacy and safety of biphasic insulin aspart 30/70 (BIAsp 30) plus pioglitazone (n = 93), glibenclamide (glyburide) plus pioglitazone (n = 91), or BIAsp 30 monotherapy (n = 97). METHODS: This 18-week, multinational, multicenter, randomized, open-label, parallel-group trial involved 281 patients with type 2 diabetes (60% male; mean age, 56 years; mean body mass index, 29.5 kg/m2) with inadequate glycemic control (mean glycosylated hemoglobin [HbA(1c)], 9.5%; range, 7.4%-14.7%) on glibenclamide monotherapy or combination therapy. The primary objective was to compare end-of-trial HbA(1c) among the 3 treatment groups. Fasting and mean 7- and 8-point blood glucose profiles, blood lipid levels, plasminogen activator inhibitor levels, adverse events, and hypoglycemia frequency were also compared. Patients using BIAsp 30 (alone or with pioglitazone) were injected twice daily (immediately before breakfast and dinner). Pioglitazone (30 mg/d) and glibenclamide (5-15 mg/d) were taken orally once daily with or immediately after breakfast. RESULTS: At the end of the trial, HbA(1c) was significantly lower for the BIAsp 30 plus pioglitazone group than for the glibenclamide plus pioglitazone group (mean [SD], -0.64% [0.23%]; P = 0.005) and the BIAsp 30 monotherapy group (-0.60% [0.22%]; P = 0.008). Mean (SD) fasting blood glucose (before breakfast) was significantly lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone (153 [45] mg/dL vs 169 [65] mg/dL, respectively; P = 0.012). Each time point on the 8-point blood glucose profile was lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone (P < 0.001 to P < 0.05). No major hypoglycemic episodes were reported, and the absolute rate of hypoglycemic events was low (<1 event/patient-week) in the BIAsp-only group. Edema was reported in < or =9% of patients in each treatment group, but no occurrence was classified as serious. Weight gain (mean, 4.0 kg) was more common in the BIAsp plus pioglitazone group (8%); however, this was consistent with improved glycemic control and is similar to that reported in other pioglitazone trials. CONCLUSIONS: BIAsp 30 plus pioglitazone provided an efficacious and well-tolerated treatment alternative to glibenclamide plus pioglitazone or BIAsp 30 alone in this population of patients who previously were not well controlled on glibenclamide monotherapy or combination therapy.     

Erectile function and gonadal hormones levels in men with end‐stage renal disease: It's relevance to duration of haemodialysis

In this study, we evaluated the relationship between haemodialysis (HD) duration and erectile function status and gonadal hormones serum levels in adult men with end‐stage renal disease (ESRD). A total of 118 men with ESRD on chronic HD were eligible for analysis. The erectile dysfunction (ED) was defined and graded according to the international index of erectile function (IIEF‐5) score. The serum levels of follicle stimulating hormones (FSH), luteinising hormone (LH), testosterone (TST), prolactin (PRL) and estradiol (E2) were measured using the standard laboratory technique. The mean age was 48.97 ± 14.68 years and mean duration of HD was 4.58 ± 3.03 years. The overall prevalence of ED was 78.8%; from them 31.2% had severe grade. The prevalence of ED was comparable in HD duration categories [≤5 years (79.7%), 5–10 years (76.5%), >10 years (80.0%); p > 0.05]. The percentage of abnormal serum levels of FSH, LH, TST, PRL, E2 were 5.1%, 1.6%, 18.6%, 90.7% and 0.0% respectively. No significant relationships were observed between HD duration and IIEF‐5 score or gonadal hormones serum levels (p < 0.05). We concluded that HD duration has no effect on erectile function status and gonadal hormones serum levels. Other factors may be relevant to these conditions in this particular group of patients.     

RNaseH2 mutants that cause Aicardi–Goutieres syndrome are active nucleases

Mutations in the genes encoding the RNaseH2 and TREX1 nucleases have been identified in patients with Aicardi–Goutieres syndrome (AGS). To determine if the AGS RNaseH2 mutations result in the loss of nuclease activity, the human wild-type RNaseH2 and four mutant complexes that constitute the majority of mutations identified in AGS patients have been prepared and tested for ribonuclease H activity. The heterotrimeric structures of the mutant RNaseH2 complexes are intact. Furthermore, the ribonuclease H activities of the mutant complexes are indistinguishable from the wild-type enzyme with the exception of the RNaseH2 subunit A (Gly37Ser) mutant, which exhibits some evidence of altered nuclease specificity. These data indicate that the mechanism of RNaseH2 dysfunction in AGS cannot be simply explained by loss of ribonuclease H activity and points to a more complex mechanism perhaps mediated through altered interactions with as yet identified nucleic acids or protein partners.     

Trend towards multiple authorship in occupational medicine journals

Background  

There is an established trend towards an increasing number of authors per article in prestigious journals for medicine and health sciences. It is uncertain whether a similar trend occurs to the same extent in journals for specific medical specialties.     

Botulinum toxin treatment for overactive bladder: Risk of urinary retention

In recent years, botulinum-A neurotoxin has increasingly been used to manage lower urinary tract symptoms, including overactive bladder and detrusor overactivity (DO), either due to neurogenic or idiopathic etiology. Techniques, doses, and preparation vary. Although many studies have reported promising results regarding efficacy, potential adverse effects, particularly urinary retention, have been less comprehensively reported. We performed a critical review of published studies evaluating botulinum treatment for overactive bladder and its reported effects on voiding function. Acute urinary retention is recognized, though rare. Chronic urinary retention is inconsistently reported; it appears to be more common in neurogenic DO, but it can occur in idiopathic DO. Increased postvoid residuals have been reported by several studies, but the clinical significance that investigators attach to the observation varies. The detrimental effect of retention on quality of life can be considerable. Accordingly, patients should be fully counseled on the risks of urinary retention and trained in intermittent catheterization before the procedure. Postvoid residual assessment should be part of follow-up and patients should be warned of possible presentations.     

The IMPROVE study--a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts

Aims: The IMPROVE? study is a multinational, open‐label, non‐randomised, 26‐week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians’ treatment decisions. Methods: Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen. Results: Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target‐setting for postprandial glucose levels was variable. A twice‐daily regimen was used to start BIAsp 30 therapy for 80% or more of patients. Conclusions: The IMPROVE? baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians’ choice of BIAsp 30, this was not consistently reflected in the targets set.