Observational study of the association of first insulin type in uncontrolled type 2 diabetes with macrovascular and microvascular disease

<p>Aims: To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.</p> <p>Methods: People included in THIN United Kingdom primary care record database who began insulin (2000–2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A1c (HbA1c) and weight change.</p> <p>Results: Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA1c had reduced less in basal versus pre-mix or NPH at 6–8 and at 9–11 months, and versus pre-mix at 12–14 months.</p> <p>Conclusion: We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA1c compared to other insulins.</p&gt

Contact frequency determines outcome of basal insulin initiation trials in type 2 diabetes

Aims/hypothesis The aim of the present study was to investigate whether predetermined contact frequency with the study teamand endpoint insulin dose are associated with study outcomes in basal insulin initiation trials in type 2 diabetes. Methods A systematic Medline search was performed. Using data from the selected studies, contact frequency was plotted against HbA(1c) reduction and endpoint insulin dose. The importance of face-to-face vs telephone contact was also analysed. Insulin dose was plotted against HbA(1c) reduction, hypoglycaemia rate and weight gain. To investigate non-specific study effects, the relationship between contact frequency and HbA(1c) was also assessed in dipeptidyl peptidase-4 (DPP-4) inhibitor trials. Results The reduction in HbA(1c) was highly correlated with contact frequency and endpoint insulin dose (r(2)=0.751, p<0.001 and r(2)=0.433, p=0.008, respectively). However, after adjusting for contact frequency, the relationship between insulin dose and HbA(1c) reduction was no longer significant (p=0.270). The frequency of both clinical and telephone contacts were independent predictors of HbA(1c) improvement (p=0.010 and p<0.001, respectively). We found no dose response relationship between end-of-study insulin dose and hypoglycaemia or weight gain. In DPP-4 inhibitor studies, contact frequency was not positively associated with HbA(1c). Conclusions/interpretation The frequency of contact with the study team is highly correlated with the improvement in HbA(1c) achieved in basal insulin initiation trials in type 2 diabetic patients. This has important implications for trial design and interpretation, as well as for clinical car

Glargine and degludec: solution behaviour of higher dose synthetic insulins

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers (“multi-hexamerisation”). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24–40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

An explorative qualitative study to determine the footwear needs of workers in standing environments

Background: Many work places require standing for prolonged periods of time and are potentially damaging to health, with links to musculoskeletal disorders and acute trauma from workplace accidents. Footwear provides the only interaction between the body and the ground and therefore a potential means to impact musculoskeletal disorders. However, there is very limited research into the necessary design and development of footwear based on both the physical environmental constraints and the personal preference of the workers. Therefore, the purpose of this study is to explore workers needs for footwear in the ‘standing’ workplace in relation to MSD, symptoms, comfort and design. Method: Semi-structured interviews were conducted with participants from demanding work environments that require standing for high proportions of the working day. Thematic analysis was used to analyse the results and gain an exploratory understanding into the footwear needs of these workers. Results: Interviews revealed the environmental demands and a very high percentage of musculoskeletal disorders, including day to day discomfort and chronic problems. It was identified that when designing work footwear for standing environments, the functionality of the shoe for the environment must be addressed, the sensations and symptoms of the workers taken into account to encourage adherence and the decision influencers should be met to encourage initial footwear choice. Meeting all these criteria could encourage the use of footwear with the correct safety features and comfort. Development of the correct footwear and increased education regarding foot health and footwear choice could help to reduce or improve the effect of the high number of musculoskeletal disorders repeatedly recorded in jobs that require prolonged periods of standing. Conclusion: This study provides a unique insight into the footwear needs of some workers in environments that require prolonged standing. This user based enquiry has provided information which is important to workplace footwear design