The Burden and Impacts of Mealtime Insulin from the Perspective of People with Diabetes.

INTRODUCTION: While there have been continued advances in insulin treatment for diabetes since the discovery of insulin 100 years ago, some unmet needs still remain, including those related to mealtime insulin (MTI). The objective of this study was to explore the impacts related to MTI and the relative burden of the impacts on people with diabetes. METHODS: This study was conducted across two phases, namely, a qualitative and quantitative phase. People with type 1 and 2 diabetes using MTI in the USA and UK were recruited for the study. The qualitative phase involved 30 interviews to explore the impacts associated with MTI. Based on the results of the qualitative phase, a list of impacts was developed to evaluate the importance of MTI impacts using best-worst scaling. RESULTS: A total of 30 participants completed interviews, and 336 completed the quantitative phase. Participants described a range of impacts associated with MTI, including psychological (72.0%), social (63.0%), work/school (53.8%), and sleep (51.7%). Impacts for the quantitative phase were categorized under the following domains: diabetes distress, diabetes management, work productivity, and social. The three most burdensome impacts were related to diabetes distress, but the diabetes management domain contributed more than diabetes distress to the relative burden. There were minor differences in the relative importance of impacts by diabetes type, diabetes duration, and experience with continuous glucose monitoring. CONCLUSION: This study confirms that people with diabetes using MTI still have an array of unmet needs, including those related to the management of their diabetes and the emotional distress of having diabetes. These findings may be useful for healthcare provider (HCP)-patient interactions to ensure HCPs are allowing patients an opportunity to discuss their experiences with MTI.

Estimated glomerular filtration rate progression in UK primary care patients with type 2 diabetes and diabetic kidney disease: a retrospective cohort study.

AIMS: To examine the rates of diabetic kidney disease (DKD) progression and associated factors, we undertook a study of estimated glomerular filtration rate (eGFR) in a historical cohort of UK primary care patients with type 2 diabetes mellitus (T2DM) and associated DKD from the Clinical Practice Research Datalink. METHODS: Our eligible population were patients with definitive T2DM from a recorded diagnostic code with either a diagnosis of chronic kidney disease (CKD) or renal function test values and renal abnormalities consistent with a CKD diagnosis, identified between 1 October 2006 and 31 December 2011. Only patients with albuminuria results reported in mg/l were used for the longitudinal statistical analyses of the eGFR rate of change using multilevel models. RESULTS: We identified 111,030 patients with T2DM. Among them 58.6% (95% confidence interval (CI): 58.3-58.9) had CKD and 37.2% (95% CI: 36.9-37.5%) had presumed DKD at baseline. Only 19.4% of patients had urinary albumin test results expressed as mg/l in the year prior to index date. Almost two-thirds (63.8%) of patients with T2DM and presumed DKD received prescriptions for angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor blockers (ARB) or both. Time-dependent variables that predict subsequent eGFR decline include increased albuminuria, time from index date and older age. CONCLUSION: Only a minority of diabetic patients with DKD had quantitative albuminuria assessments. The relatively low proportion of DKD patients with ACEi or ARB prescriptions suggests a gap between healthcare practice and available scientific evidence during the study period. Increased albuminuria and older age were the most consistent predictors of subsequent eGFR decline.

Is the current standard of care leading to cost-effective outcomes for patients with type 2 diabetes requiring insulin? A long-term health economic analysis for the UK.

AIMS: The aim of the analysis was to investigate whether insulin intensification, based on the use of intensive insulin regimens as recommended by the current standard of care in routine clinical practice, would be cost-effective for patients with type 2 diabetes in the UK. METHODS: Clinical data were derived from a retrospective analysis of 3185 patients with type 2 diabetes on basal insulin in The Health Improvement Network (THIN) general practice database. In total, 48% (614 patients) intensified insulin therapy, defined by adding bolus or premix insulin to a basal regimen, which was associated with a reduction in HbA1c and an increase in body mass index. Projections of clinical outcomes and costs (2011 GBP) over patients' lifetimes were made using a recently validated type 2 diabetes model. RESULTS: Immediate insulin intensification was associated with improvements in life expectancy, quality-adjusted life expectancy and time to onset of complications versus no intensification or delaying intensification by 2, 4, 6, or 8 years. Direct costs were higher with the insulin intensification strategy (due to the acquisition costs of insulin). Incremental cost-effectiveness ratios for insulin intensification were GBP 32,560, GBP 35,187, GBP 40,006, GBP 48,187 and GBP 55,431 per QALY gained versus delaying intensification 2, 4, 6 and 8 years, and no intensification, respectively. CONCLUSIONS: Although associated with improved clinical outcomes, insulin intensification as practiced in the UK has a relatively high cost per QALY and may not lead to cost-effective outcomes for patients with type 2 diabetes as currently defined by UK cost-effectiveness thresholds.

A comprehensive review of predictive and prognostic composite factors implicated in the heterogeneity of treatment response and outcome across disease areas.

AIM: To assess and present the current body of evidence regarding composite measures associated with differential treatment response or outcome as a result of patient heterogeneity and to evaluate their consistency across disease areas. METHODS: A comprehensive review of the literature from the last 10 years was performed using three databases (PubMed, Embase and Cochrane). All articles that met the inclusion/exclusion criteria were selected, abstracted and assessed using the NICE level-of-evidence criteria. RESULTS: Forty-nine studies were identified in the data abstraction. Approximately one-third focused on existing composite measures, and the rest investigated emerging composite factors. The majority of studies targeted patients with cancer, cardiovascular disease or psychological disorders. As a whole, the composite measures were found to be disease-specific, but some composite elements, including age, gender, comorbidities and health status, showed consistency across disease areas. To complement these findings, common individual factors found in five previous independent disease-specific literature assessments were also summarised, including age, gender, treatment adherence and satisfaction, healthcare resource utilisation and health status. CONCLUSIONS: Composite measures can play an important role in characterising heterogeneity of treatment response and outcome in patients suffering from various medical conditions. These measures can help clinicians to better distinguish between patients with high likelihood to respond well to treatment and patients with minimal chances of positive therapeutic outcomes. Herein, the individual factors identified can be used to develop novel predictive or prognostic composite measures that can be applicable across disease areas. Reflecting these cross-disease measures in clinical and public health decisions has the distinctive appeal to enable targeted treatment for patients suffering from multiple medical conditions, which may ultimately yield significant gains in individual outcomes, population health and cost-effective resource allocation.

A review of treatment response in type 2 diabetes: assessing the role of patient heterogeneity.

The response to treatment for type 2 diabetes typically varies among individuals within a study population. This variation is known as heterogeneity of treatment response. We conducted a comprehensive literature review to identify factors that account for heterogeneity of treatment response in patients treated for type 2 diabetes. Three databases (PubMed, EMBASE and Cochrane Library) were searched for articles published in the last 10 years describing investigations of factors associated with treatment response and outcomes among people with type 2 diabetes receiving pharmacological treatment. Of the 43 articles extracted and summarized, 35 (81%) discussed clinical factors, 31 (72%) described sociodemographic factors and 17 (40%) reported on comorbidity or behavioural factors. Clinical factors identified included baseline glycated hemoglobin A1c or fasting plasma glucose (FPG) levels, insulin response or sensitivity, C-peptide, body composition, adipose tissue proteins, lipid profile, plasma albumin levels and duration of disease or insulin treatment. Other factors identified included age, sex, race, socioeconomic status and comorbidities. This review identified the following research gaps: use of multiple definitions for response, few patient-reported measures and lack of evidence regarding whether factors were associated with treatment response for only specific medications or across pharmacological therapies. Furthermore, identification of factors associated with type 2 diabetes treatment response was generally a secondary objective in the research reviewed. Understanding which patient subgroups are more likely to respond to treatment and identifying factors associated with response may result in targeted treatment decisions and alter the interpretation of efficacy or effectiveness of results. In conclusion, accounting for these factors in clinical trials and when making clinical treatment decisions may improve therapy selection and individual patient outcomes.

A formal total synthesis of dysidiolide.

[structure] A formal total synthesis of the natural product dysidiolide is described. Starting from a Diels-Alder reaction between an enoate and a Rawal diene, the cyclohexenone 4 was synthesized. A subsequent stereospecific methyl cuprate addition established the desired trans configuration in the cyclohexane 3. Wacker oxidation of the pentenyl side chain to the diketone 17 followed by an intramolecular aldol condensation led to the bicyclic enone 2, a key intermediate in a recently reported synthesis of dysidiolide.