Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men.

Higher plasma leucine, isoleucine and valine (BCAA) concentrations are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention. Fasting plasma BCAAs were quantified in an OW (n = 26; BMI 32.4 ± 3 kg/m2; mean age 44 ± 9 y) and a normal-weight (NW) group (n = 26; BMI 24 ± 3.1 kg/m2; mean age 32 ± 12.3 y). Ten of the OW group (BMI 32.2 ± 4 kg/m2; 46 ± 8 y) then underwent 6-weeks of VLCD (600-800 kcal/day). Fasting plasma BCAA (gas chromatography-mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were higher in OW individuals (sum leucine/isoleucine/valine: 457 ± 85 µM) compared to NW control individuals (365 ± 78 µM, p < 0.001). Despite significant weight loss (baseline 103.9 ± 12.3 to 93 ± 9.6 kg and BMI 32.2 ± 4 to 28.9 ± 3.6 kg/m2), no changes were observed in BCAAs after 6-weeks of VLCD. Moreover, although VLCD resulted in a significant reduction in HOMA-IR (baseline 1.19 ± 0.62 to 0.51 ± 0.21 post-VLCD; p < 0.001), Pearson's r revealed no relationships between BCAA and HOMA-IR, either before (leucine R2: 2.49e-005, p = 0.98; isoleucine R2: 1.211-e006, p = 0.9; valine R2: 0.004, p = 0.85) or after VLCD (leucine R2: 0.003, p = 0.86; isoleucine R2: 0.006, p = 0.82; valine R2: 0.002, p = 0.65). Plasma BCAA are higher in OW compared to NW individuals. However, while 6-weeks VLCD reduced body weight and IR in OW individuals, this was not associated with reductions in BCAA. This suggests that studies demonstrating links between BCAA and insulin resistance in OW individuals, are complex and are not normalised by simply losing weight.

Diversity, trait preferences, management and utilization of yams landraces (Dioscorea species): an orphan crop in DR Congo.

Yam (Dioscorea spp.) is cultivated in many villages of DR Congo as a means to sustain food security and alleviate poverty. However, the extent of the existing diversity has not been studied in details thus, considered as an orphan. A survey covering 540 farmers in 54 villages was conducted in six major yam growing territories covering three provinces in DR Congo to investigate the diversity, management and utilization of yam landraces using pre-elaborate questionnaires. Subject to synonymy, a total of 67 landraces from five different species were recorded. Farmers' challenges limiting yam production were poor tuber qualities (69%), harvest pest attack (7%), difficulty in harvesting (6%), poor soil status (6%). The overall diversity was moderate among the recorded yam germplasm maintained at the household level (1.32) and variability exist in diversity amongst the territories and provinces. Farmers' in territories of Tshopo and Mongala provinces maintained higher level of germplasm diversity (2.79 and 2.77) compared to the farmers in territories of Bas-Uélé (1.67). Some yam landraces had limited abundance and distribution due to loss of production interest in many villages attributable to poisons contained hence, resulting in possible extinction. Farmers' most preferred seed source for cultivation were backyard (43%) and exchange with neighboring farmers (31%) with the objective of meeting food security and generating income. In villages where yam production is expanding, farmers are relying on landraces with good tuber qualities and high yield even though they are late maturing. This study revealed the knowledge of yam landrace diversity, constraints to production and farmers' preferences criteria as a guide for collection and conservation of yam germplasm for yam improvement intervention.

Expert consensus on the minimum clinical standards of practice for Nigerian physiotherapists working in intensive care units: A modified Delphi study.

BACKGROUND: Management of patients in intensive care units (ICUs) needs staff with a recommended level of expertise and experience owing to the life-threatening nature of illnesses, injuries and complications that these patients present with. There are no specific guidelines governing physiotherapy practice in ICUs in Nigeria. Hence, there is a need to have expert consensus on the minimum clinical standard of practice for physiotherapists working in ICUs as a first step to proposing/developing guidelines in the future. OBJECTIVES: To assess the expert consensus on the minimum clinical standard of practice for physiotherapists working in ICUs in Nigeria. METHODS: Physiotherapists with working experience in Nigerian ICUs were purposively recruited into the present study using a modified Delphi technique. A questionnaire comprising 222 question items on the role of physiotherapy in critical care was adopted and administered to the participants over three rounds of Delphi procedure (online). Participants checked either 'essential', 'not essential' or 'unsure' for each question item. For each question item to be considered 'essential' or 'not essential', a consensus agreement ≥70% had to be met. Questions without consensus were further modified by providing definition or clarification and presented in subsequent rounds. Data were analysed descriptively. RESULTS: We recruited 26 expert physiotherapists who consented to the study and completed the first round of the study. The majority of the physiotherapists (n=24) remained in the study after the third round. A total of 178 question items were adjudged to be 'essential' after the first round, and a further 15 and three additional items were subsequently adjudged to be as 'essential' after modifying the outstanding question items during the second and third rounds, respectively. No consensus was reached for 24 items. None of the question items were ranked as 'not essential' after all the rounds. CONCLUSION: Expert consensus was achieved for a substantial number of question items regarding knowledge and skills for assessment, condition and treatment items of the questionnaire by experienced critical care physiotherapists in Nigeria.

Bullying and truancy: Predictors to sexual practices among school-going adolescents in Malaysia - a cross-sectional study.

INTRODUCTION: Adolescents' involvement in sexual practices are becoming a major public health concern in Malaysia. This study aims to determine the prevalence of sexual practices among Malaysian school-going adolescents and its predictive factors. METHODS: A cross-sectional study was carried out from April 2012 till September 2012 among 16-year-old school adolescents from two different schools. They were selected through simple random sampling and these adolescents answered a self-administered questionnaire consisting of three sections i.e. socio-demography, risk-taking behaviours and family-adolescents relationship. Data were analysed using Pearson Chi-Square test while Simple Logistic Regression and Multiple Logistic Regression were applied to determine the predictive factors. RESULTS: The prevalence of sexual practices among the adolescents was 30.1% in which they were either involved in pornography (26.8%), pre-sexual activities (8.5%) or premarital sex (2.9%). Six predictive factors associated with sexual practices among this age group were identified which were male (adjusted Odds Ratio (aOR) 2.7, 95% Confidence Interval (95%CI) 1.4 to 2.5), truancy (aOR 2.3, 95%CI 1.3 to 4.2), bully (aOR 3.5, 95%CI 1.7 to 7.3), hanging out (aOR 2.8, 95% 1.4 to 5.6), staying out late (aOR 3.2, 95%CI 1.5 to 6.8) and conflict with family (aOR 4.1, 95%CI 1.9 to 8.9). DISCUSSION: Asian background differs from the western countries and findings of this study may suggest suitable intervention programmes that can prevent high-risk sexual practices among Asian school-going adolescents.

Premixed vs basal-bolus insulin regimen in Type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data.

AIM: To evaluate the concordance between data derived from randomized controlled trial (RCT) and real-world estimates of HbA1c and weight change after 24 weeks of initiation of a basal-bolus compared with a premixed insulin regimen in people with Type 2 diabetes. METHODS: Data eight RCTs were pooled after a systematic review of studies examining basal-bolus (n = 1893) or premixed (n = 1517) regimens. Real-world data were extracted from the UK primary care dataset for people on basal-bolus (n = 7483) or premixed insulin regimens (n=10 744). The mean differences between HbA1c and weight from baseline were calculated using t-tests, while analysis of variance was used to compare the two treatment regimens. Linear regression analyses were used to determine the predictors of this change. RESULTS: Both insulin regimens were associated with HbA1c reductions (real-world data -0.28%; RCT data, -1.4%) and weight gain (real-world data, +0.27 kg; RCT data, +2.96 kg) but there were no significant differences between basal-bolus and premixed insulin. Discordances in the pattern of treatment response were observed, however, between real-world and RCT data for both insulin regimens. For any given baseline HbA1c concentration, the change in HbA1c in the RCTs was greater than in real-world conditions and for those with baseline weight above ~60 kg, RCT data showed overall weight gain in contrast to slight weight loss in the real-world population. Lastly, for both randomized controlled trial and real-world populations, while greater baseline weight was associated with reduced response to treatment, the association was much steeper in the RCT than in the real-world population. In addition, greater baseline weight was associated with greater weight reductions in both premixed insulin and basal-bolus insulin regimens, although to a lesser extent with the latter. CONCLUSION: These results highlight specific discrepancies in the HbA1c reduction and weight change in insulin regimen between real world versus RCT populations; with greater reduction in HbA1c and greater increase in weight observed in the RCT population than in the real-world population. Also, the basal-bolus regimens in both real-world and RCT populations showed greater reduction in HbA1c compared to the premix regimen (though more marked in RCTs), while the premix regimen showed greater increase in weight in real-world, as against basal-bolus in the RCT population.

Continuous subcutaneous insulin infusion (CSII) therapy at Derby Teaching Hospitals: sustained benefits in glucose control.

AIM: In the short term, continuous subcutaneous insulin infusion (CSII) has been associated with improved glycaemic control, reduced hypoglycaemia and improved quality of life (QOL). However, limited data are available on its long-term benefits, particularly in the UK. We aimed to assess the impact of CSII on longer term outcomes. METHOD: Patient-level data were obtained for CSII users at Derby Teaching Hospitals, UK. Patient confidence and satisfaction questionnaires using the Likert scale were used to assess confidence in self-management. Comparative statistics were conducted using Pearson's chi-square and Student's t-tests. RESULTS: Some 258 CSII users were identified (60.1% female, mean age 43.9 ± 13.4 years). Overall, there was significant decrease in HbA1c from 78 mmol/mol (9.3 ± 2.0%) at baseline, to 69 mmol/mol (8.5 ± 1.3%) at 6 months [mean difference (md): -0.64; 95% confidence interval (95% CI): -0.91 to -0.37; P < 0.0001]; which was sustained at 6 years of follow-up (HbA1c : 66 mmol/mol, 8.2 ± 1.3%; md: -1.07%; 95% CI: -1.45 to -0.69; P < 0.0001). One hundred and twenty-one patients (47%) responded to the survey, of whom 95 (78.5%) reported a reduction in the frequency of hypoglycaemia; 102 (84.3%) were satisfied with the quality of care received in the insulin pump service. CONCLUSION: CSII therapy led to a sustained long-term improvement in glycaemic control in addition to a reduction in self-reported hypoglycaemia.

Involvement of oxidative stress in protocatechuic acid-mediated bacterial lethality.

The involvement of oxidative stress in protocatechuic acid-mediated bacterial lethality was investigated. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) of protocatechuic acid against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are 600 and 700 µg/ml, 600 and 800 µg/ml, and 600 and 800 µg/ml, respectively. The optical densities and colony-forming units of protocatechuic acid-treated bacteria decreased in time-dependent manner. Protocatechuic acid (4× MIC) significantly increased the superoxide anion content of E. coli, P. aeruginosa, and S. aureus compared to dimethyl sulfoxide (DMSO). Superoxide dismutase, catalase, and NAD+ /NADH in protocatechuic acid-treated E. coli, P. aeruginosa, and S. aureus increased significantly when compared to DMSO. Conversely, level of reduced glutathione decreased in protocatechuic acid-treated E. coli, P. aeruginosa, and S. aureus, while glutathione disulfide increased when compared to DMSO. Furthermore, malondialdehyde and fragmented DNA increased significantly following exposure to protocatechuic acid. Protocatechuic acid inhibited the activity of complexes I and II. From the above findings, protocatechuic acid enhanced the generation of reactive oxygen species (superoxide anion radical and hydroxyl radical) in E. coli, P. aeruginosa, and S. aureus, possibly by autoxidation, fenton chemistry, and inhibiting electron transport chain resulting in lipid peroxidation and DNA fragmentation and consequentially bacterial cell death.

Comparison of cardiovascular and metabolic outcomes in people with type 2 diabetes on insulin versus non-insulin glucose-lowering therapies (GLTs): A systematic review and meta-analysis of clinical trials.

OBJECTIVES: To compare the cardiovascular and metabolic outcomes of Insulin versus non-insulin glucose lowering therapy (GLT). METHODS: We included randomised control trials (RCTs) which randomised patients aged >18years with Type 2 Diabetes (T2D) to insulin vs non-insulin GLT. We used risk ratios (RR), risk difference (RD) and odds ratios (OR) with 95% confidence interval (95%CI) to analyse the treatment effects of dichotomous outcomes and mean differences (with 95% CI) for continuous outcomes. RESULTS: We included 18 RCTs with 19,300 participants. There was no significant difference in the risk of all-cause mortality and CV events between the groups (RR=1.01; 95%CI: 0.96-1.06; p=0.69). In 16 trials, insulin showed greater efficacy in glycaemic control (mean diff=-0.20; 95%CI: -0.28 to -0.11) but the proportion achieving HbA1c level of either ⩽7.0% or 7.4% (53 or 57mmol/mol) was similar in both (OR=1.55; 95%CI=0.92-2.62). The non-insulin group had a significant reduction in weight (mean diff=-3.41; 95%CI: -4.50 to -2.32) and an increase in the proportion of adverse events (54.7% vs 45.3%, p=0.044), but the insulin group showed an (RR=1.90; 95%CI: 1.44-2.51) increased risk of hypoglycaemia. CONCLUSION: There was no difference in the risk of all-cause mortality and adverse cardiovascular (CV) events between Insulin and non-insulin GLTs. Insulin was associated with superior reduction in HbA1c; least reduction in weight and higher risk of hypoglycaemia. Both showed similar proportion of patients achieving HbA1c target. Non-insulin GLTs were associated with a higher risk in reported adverse drug events.

Relationship between HbA1c and cancer in people with or without diabetes: a systematic review.

AIM: To identify the relationship between HbA1c and cancers in people with or without diabetes. BACKGROUND: Cancer is a major public health problem, accounting for 8.2 million deaths worldwide in 2012. HbA1c level has been associated with the risk of developing certain cancers, although the existing evidence is conflicting. METHODS: EMBASE, MEDLINE, CINAHL and the Cochrane Library were searched. Eligible articles included randomized controlled trials, cohort studies, case-control studies, systematic reviews and meta-analyses. Participants of either sex, with or without Type 1 or 2 diabetes, were included. The studies were assessed using the Scottish Intercollegiate Guidelines Network (SIGN) criteria by two independent assessors. No meta-analysis was performed because of the heterogeneity of results. RESULTS: A total of 19 studies from 1006 met the inclusion criteria, of which 14 were cohort studies and five were nested case-control studies. Eight studies investigated outcomes for all cancer sites. Four of these studies reported that higher HbA1c levels were associated with higher incidence and/or mortality risk for all cancers. One study observed a U-shaped relationship between HbA1c and cancer incidence and mortality. Increasing HbA1c levels were associated with increasing risk of developing colorectal, pancreatic, respiratory and female genital tract cancers. No increased risk was observed for breast cancer, gastrointestinal or urological malignancies. CONCLUSION: HbA1c appears to be associated with cancer incidence and/or cancer mortality, but further studies are needed to fully understand the complex relationship between HbA1c and cancer.

Drug-Induced Diabetes Mellitus: Evidence for Statins and Other Drugs Affecting Glucose Metabolism.

Abnormalities of glucose metabolism and glucose tolerance, either because of a reduction in tissue sensitivity to insulin (e.g., in liver, skeletal muscle, and adipose tissues) and/or a reduction in pancreatic insulin secretion, are associated with a number of unwanted health outcomes. Even small increases in circulating glucose levels (often described as dysglycemia or prediabetes) may confer an increased risk of cardiovascular (CV) disease and progression to overt type 2 diabetes. A number of drug therapies, many of them used long term in chronic disease management, have adverse effects on glucose metabolism, diabetes risk, and glycemic control among patients with preexisting diabetes. In this study, we review the evidence, underlying mechanisms, and the clinical significance of drug-related adverse effects on glucose metabolism.

Promoting health and reducing costs: a role for reform of self-monitoring of blood glucose provision within the National Health Service.

AIM: To determine the cost-effectiveness of all options for the self-monitoring of blood glucose funded by the National Health Service, providing guidance for disinvestment and testing the hypothesis that advanced meter features may justify higher prices. METHODS: Using data from the Health and Social Care Information Centre concerning all 8 340 700 self-monitoring of blood glucose-related prescriptions during 2013/2014, we conducted a cost-minimization analysis, considering both strip and lancet costs, including all clinically equivalent technologies for self-monitoring of blood glucose, as determined by the ability to meet ISO-15197:2013 guidelines for meter accuracy. RESULTS: A total of 56 glucose monitor, test strip and lancet combinations were identified, of which 38 met the required accuracy standards. Of these, the mean (range) net ingredient costs for test strips and lancets were £0.27 (£0.14-£0.32) and £0.04 (£0.02-£0.05), respectively, resulting in a weighted average of £0.28 (£0.18-£0.37) per test. Systems providing four or more advanced features were priced equal to those providing just one feature. A total of £12 m was invested in providing 42 million self-monitoring of blood glucose tests with systems that fail to meet acceptable accuracy standards, and efficiency savings of £23.2 m per annum are achievable if the National Health Service were to disinvest from technologies providing lesser functionality than available alternatives, but at a much higher price. CONCLUSION: The study uncovered considerable variation in the price paid by the National Health Service for self-monitoring of blood glucose, which could not be explained by the availability of advanced meter features. A standardized approach to self-monitoring of blood glucose prescribing could achieve significant efficiency savings for the National Health Service, whilst increasing overall utilisation and improving safety for those currently using systems that fail to meet acceptable standards for measurement accuracy.

Semianalytical approach to criteria for ignition of excitation waves.

We consider the problem of ignition of propagating waves in one-dimensional bistable or excitable systems by an instantaneous spatially extended stimulus. Earlier we proposed a method [I. Idris and V. N. Biktashev, Phys. Rev. Lett. 101, 244101 (2008)] for analytical description of the threshold conditions based on an approximation of the (center-)stable manifold of a certain critical solution. Here we generalize this method to address a wider class of excitable systems, such as multicomponent reaction-diffusion systems and systems with non-self-adjoint linearized operators, including systems with moving critical fronts and pulses. We also explore an extension of this method from a linear to a quadratic approximation of the (center-)stable manifold, resulting in some cases in a significant increase in accuracy. The applicability of the approach is demonstrated on five test problems ranging from archetypal examples such as the Zeldovich-Frank-Kamenetsky equation to near realistic examples such as the Beeler-Reuter model of cardiac excitation. While the method is analytical in nature, it is recognized that essential ingredients of the theory can be calculated explicitly only in exceptional cases, so we also describe methods suitable for calculating these ingredients numerically.

Biphasic vs basal bolus insulin regimen in Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

AIM: We aim to evaluate the effects of biphasic insulin compared with a basal bolus insulin regimen on glycaemic control, total daily insulin requirements, risk of hypoglycaemia, weight and quality of life in patients with diabetes mellitus. METHODS: MEDLINE, EMBASE, PubMed and Scopus databases were searched for studies up to November 2013. Interventions that lasted for more than four weeks and were reported in English were considered for the review. Meta-analysis was performed on eligible studies. RESULTS: Fifteen randomized controlled trial studies, involving 4384 patients, were included. Greater HbA1c reductions were seen with basal-bolus compared with biphasic insulin regimens, between-treatment weighted mean difference (WMD) for baseline-to-endpoint changes in HbA1c was -0.2% (95% CI: -0.36 to -0.03) [-2.2 (-3.9, -0.3) mmol/mol]. In non-insulin naïve (n = 8) patients with Type 2 diabetes, HbA1c reduction was greater in the basal bolus group; WMD = -0.22% (95% CI: -0.42 to -0.02) [-2.4 (-4.6, -0.2) mmol/mol], but in insulin naïve patients (n = 5), HbA1c was equivalent between the two regimens; WMD (-0.15% (95% CI: -0.52 to 0.22) [-1.6 (-5.7, 2.4) mmol/mol]. Total daily insulin requirements and weight were increased with both regimens, whereas hypoglycaemia rates were comparable between the two regimens. Greater HbA1c reduction was observed in the basal bolus group compared with the biphasic regimen at the expense of higher daily insulin requirements and weight gain, but with no greater risk of hypoglycaemia. CONCLUSIONS: Biphasic and basal bolus regimens were equally effective in reducing HbA1c in insulin naïve patients with Type 2 diabetes and both regimens are equally effective for initiating insulin in Type 2 diabetes.

Clinical use and efficacy of biphasic insulin lispro 50/50 in people with insulin treated diabetes - a nationwide evaluation of clinical practice.

OBJECTIVES: This study aims to investigate the metabolic effects of biphasic insulin lispro 50/50 in routine clinical practice. A total of 229 patients who were ≥18 years old with diabetes, newly treated with biphasic insulin lispro 50/50, were sourced from six secondary care services in England. METHODS: Detailed clinical parameters were compared at baseline, and 3 and 6 months post-initiation. Responders was defined as those with HbA1c <7.5% (58 mmol/mol) and/or an HbA1c reduction of >1% (11 mmol/mol) at 6 months. RESULTS: HbA1c showed significant reduction: -0.93% (-10 mmol/mol) and -1.2% (-13 mmol/mol) at 3 and 6 months respectively, while no significant change was noted for all the other parameters. When analyzed according to frequencies of injections/day, the greatest reduction was observed with the three times a day regimen (-1.0% [-11.0 mmol/mol] and -1.3% [-14.6 mmol/mol] at 3 and 6 months respectively). HbA1c reduction was greatest in the group who previously received a basal-bolus insulin regimen: (-0.8% [-9.0 mmol/mol] and -1.5% [-16.2 mmol/mol] at 3 and 6 months respectively). Reduction in weight was observed at 3 months (-1.8 kg ± 4.3) only for those who were previously on a basal-bolus insulin regimen. Insulin doses increased following conversion to biphasic insulin lispro 50/50, irrespective of the types of insulin used prior to biphasic insulin lispro 50/50, but this was not associated with weight gain. The independent predictors of response to biphasic insulin lispro 50/50 were baseline HbA1c, Caucasian, presence of nephropathy, prior use of basal-bolus insulin and prior use of other premixed combination. CONCLUSION: Biphasic insulin lispro 50/50 is therefore an effective therapeutic option for achieving glycemic control in patients with suboptimal HbA1c levels, especially among those who were previously on a basal-bolus insulin regimen and those who received it three times daily, with a neutral effect on weight parameters. LIMITATIONS: This was a retrospective study of routine clinical practice and is therefore limited by allocation bias and some missing data. Information on rates of hypoglycemia and quality of life are not available.

Post-Traumatic Stress Disorder And Its Associated Factors Among School-Going Children Exposed To A Tsunami Disaster In Malaysia

Posttraumatic stress disorder (PTSD) is a psychiatric diagnosis made when someone including children who experiences traumatic stressor. Those who are exposed to a more severe trauma have highest level of PTSD. The aim of this study was to measure the prevalence of PTSD and its associated factors among 219 children who were affected by a form of natural disaster which is the tsunami waves in a rural area in Malaysia. A cross sectional study was carried out among children aged 10-12 years 6 months after the traumatic event. Child Posttraumatic Stress Disorder –Reaction Index (CPTSD-RI) was used as a screening instrument which was answered by the affected children through a self-administered questionnaire. Forty six percent of these children had PTSD symptoms; 31.1% of these children had mild, 11.4% had moderate, 3.7% had severe PTSD and none had very severe PTSD. Result also showed that 91.8% had re-experiencing symptoms, 28.3% had numbing/avoidance symptoms and 49.3% had hyperarousal symptoms. Children with low social support (Adj OR = 2.3 (95% CI: = 1.3- 4.2)), and children who experienced deaths among someone close to them (Adj OR = 3.7 (95% CI =1.2 - 11.5)) were more likely to have symptoms of PTSD. This showed that children are at higher risk of developing PTSD as early as 6 months after the event and thus early intervention should be offered to them. Future longitudinal study can be carried out among affected children to assess whether these PTSD symptoms persist over time.

Obesity independently predicts responders to biphasic insulin 50/50 (Humalog Mix50 and Insuman Comb 50) following conversion from other insulin regimens: a retrospective cohort study.

AIMS: This study aims to examine the metabolic effects of intensification or initiation of insulin treatment with biphasic insulin 50/50, and determine the predictors of responders or non-responders to biphasic insulin 50/50. METHODS: A cohort of 2183 patients ≥18 years with diabetes, newly treated with biphasic insulin 50/50 between January 2000 and May 2012, were sourced from UK General Practices via The Health Improvement Network (THIN) database. Baseline clinical parameters of 1267 patients with suboptimal glycated hemoglobin (HbA1c) >7.5% (>58 mmol/mol) who had received background insulin regimens for at least 6 months preceding biphasic insulin 50/50 were compared against 12-month outcome data. Responders were defined as those with HbA1c <7.5% (58 mmol/mol) and/or HbA1c reduction of ≥1% (10.9 mmol/mol) at 12 months. Comparative analyses were carried out on subgroups of 237 patients initiating insulin therapy with biphasic insulin 50/50, and between users of the Humalog Mix50 (HM50) versus Insuman Comb 50 (IC50). Associations were examined using t tests and multivariate logistic regression techniques. RESULTS: The overall mean HbA1c reduction at 12 months as a result of intensification and initiation with biphasic insulin 50/50 was 0.5% (5.5 mmol/mol) and 1.6% (17.5 mmol/mol), respectively. Adjusted ORs show obesity (body mass index >30 kg/m(2)), treatment duration for ≥9 months, and baseline HbA1c are independent determinants of responders. In addition, stratified for baseline HbA1c levels, HM50 was associated with better HbA1c outcome compared with IC50. CONCLUSIONS: biphasic insulin 50/50 is effective for achieving glycemic control in suboptimal HbA1c levels, especially among obese patients with insulin-treated diabetes. Stratified for baseline HbA1c, HM50 was associated with improved HbA1c outcome compared with IC50.

The use of U-500 regular insulin in the management of patients with obesity and insulin resistance.

The rise in prevalence of obesity and diabetes has created a challenge in managing increasing numbers of patients who require high doses of insulin. This article reviews the published literature on the properties of U-500 insulin and its use in clinical practice. U-500 insulin is likely to have a longer time to peak effect and a longer duration of action than similar doses of U-100 insulin. Evidence for its use in clinical practice rests on retrospective case series, which suggests that the use of U-500 insulin either by multiple daily injections or a continuous subcutaneous insulin infusion is effective in improving glycaemic control. To prevent insulin dosing and administration errors, great care must be taken in providing staff and patient education, and in developing policies for the management of patients on U-500 insulin who are admitted to hospital.

The effects of polymorphisms in 7 candidate genes on resistance to Salmonella Enteritidis in native chickens.

Salmonella enterica serovar Enteritidis infection is a common concern in poultry production for its negative effects on growth as well as food safety for humans. Identification of molecular markers that are linked to resistance to Salmonella Enteritidis may lead to appropriate solutions to control Salmonella infection in chickens. This study investigated the association of candidate genes with resistance to Salmonella Enteritidis in young chickens. Two native breeds of Malaysian chickens, namely, Village Chickens and Red Junglefowl, were evaluated for bacterial colonization after Salmonella Enteritidis inoculation. Seven candidate genes were selected on the basis of their physiological role in immune response, as determined by prior studies in other genetic lines: natural resistance-associated protein 1 (NRAMP1), transforming growth factor ß3 (TGFß3), transforming growth factor ß4 (TGFß4), inhibitor of apoptosis protein 1 (IAP1), caspase 1 (CASP1), lipopolysaccharide-induced tumor necrosis factor (TNF) α factor (LITAF), and TNF-related apoptosis-inducing ligand (TRAIL). Polymerase chain reaction-RFLP was used to identify polymorphisms in the candidate genes; all genes exhibited polymorphisms in at least one breed. The NRAMP1-SacI polymorphism correlated with the differences in Salmonella Enteritidis load in the cecum (P = 0.002) and spleen (P = 0.01) of Village Chickens. Polymorphisms in the restriction sites of TGFß3-BsrI, TGFß4-MboII, and TRAIL-StyI were associated with Salmonella Enteritidis burden in the cecum, spleen, and liver of Village Chickens and Red Junglefowl (P < 0.05). These results indicate that the NRAMP1, TGFß3, TGFß4, and TRAIL genes are potential candidates for use in selection programs for increasing genetic resistance against Salmonella Enteritidis in native Malaysian chickens.

Responders to insulin therapy at 18 months in adults with newly diagnosed diabetes: which insulin regimen?

OBJECTIVES: To describe baseline characteristics of responders to insulin therapy (HbA(1c) targets < 58 mmol/mol, 7.5%) at 18 months among adults with newly diagnosed diabetes. METHODS: A retrospective UK study derived from 479 general practices electronic dataset. We included all adults (age > 18 years) with newly diagnosed diabetes who required insulin therapy within 6 months of diagnosis. The data comprised insulin regimen (long-acting only; premixed insulin only; basal bolus insulin regimen), gender, Townsend quintile, baseline and an 18-month measurement of clinical and biochemical variables. Multiple imputations were undertaken and logistic regression used to assess the effect of covariates. RESULTS: A total of 1492 patients (aged 19-93 years) were analysed. Means (SD) baseline HbA(1c) and BMI were 10.3% (2.6%) and 29.6 (7.0%), respectively. Following multiple imputation for missing data, logistic regression analysis indicated important covariates to achieve HbA(1c) targets were baseline HbA(1c), lipid lowering therapy, gender and age. Including all covariates, those treated with premixed insulin were 47% more likely to achieve target HbA(1c) at 18 months than those treated with a basal-bolus regimes (adjusted OR 1.47; 95% CI 1.12-1.92, P = 0.006)) and 32% more likely than those treated with long-acting insulin was (adjusted OR 1.32; 95% CI 1.01-1.74, P = 0.044). Those with a higher baseline HbA(1c) level, on lipid-lowering therapy, women and younger patients had a lower response rate. Mean weight gain (SD) was 2.4 kg (8.5 kg) and was not influenced by treatment regimen. CONCLUSION: The use of premixed insulin regimen among newly diagnosed patients with diabetes appears to be most effective in reaching HbA(1c) target values, independent of other confounders. The appropriate choice of insulin regimen at initiation should therefore take into account various metabolic and psychosocial factors.