Living with sub-optimal glycaemic control: the experiences of Type 2 diabetes diagnosis and education

Aim The aim of this study was to explore the experiences of diagnosis and education for people living with Type 2 diabetes who have sub-optimal glycaemic control. Background The increasing prevalence of Type 2 diabetes is a global concern. Many people have difficulty maintaining optimal glycaemic control with up to 50% having HbA1c levels higher than recommended. A range of factors that have been suggested as possibly contributing to this, however, little is known about how their experience of diagnosis, education and support to attempt to understand the context of their self-management practices. Design A qualitative thematic analysis of interviews conducted with people with sub-optimal glycaemic control prior to their participation in an intervention study. Method Thirty participants taking part in a psychosocial/educational intervention for people with sub-optimal glycaemic control were interviewed in 2012 before the intervention commenced. These interviews explored each participant's experience of the diagnosis and associated education. The interviews were transcribed and a thematic analysis was conducted. Findings Almost all the participants had been shocked at receiving the diagnosis and felt it had been a moral indictment on their lifestyle. Many had been given the impression that they had a mild form of diabetes and most had been given very little information on self-management that they had found useful. Conclusion The findings suggest that for the participants there was a considerable gap between the rhetoric of person-centred services and the reality of the experiences of diagnosis and education for the self-management of Type 2 diabetes

A nurse-led education and cognitive behaviour therapy-based intervention among adults with uncontrolled type 2 diabetes: A randomised controlled trial

Rationale, aims and objectives: Diabetes mellitus is associated with significant morbidity, mortality and escalating healthcare costs. Research has consistently demonstrated the importance of glycaemic control in delaying the onset, and decreasing the incidence, of both the short- and long-term complications of diabetes. Although glycaemic control is difficult to achieve and challenging to maintain, it is key to reducing negative disease outcomes.  The aim of this study was to determine whether a nurse-led educational intervention alone or a nurse-led intervention using education and acceptance and commitment therapy (ACT) were effective in reducing HbA1c in people living with uncontrolled type 2 diabetes compared to usual care.  Methods: Adults over the age of 18 years, with a confirmed diagnosis of type 2 diabetes and HbA1c outside of the recommended range (4-7%, 20-53 mmol/mol) for 12 months or more were eligible to participate.  Participants were randomised to either a nurse-led education intervention, a nurse-led education plus ACT intervention or usual care. One hundred and eighteen participants completed baseline data collection (N=34 education group, N=39 education plus ACT, N=45 control group). An intention to treat analysis was employed.  Results: A statistically significant reduction in HbA1c in the education intervention group was found (p=.011 [7.48, 8.14]). At 6 months, HbA1c was reduced in both intervention groups (Education group -0.21, education and ACT group -0.04) and increased in the control group (+0.32). A positive change in HbA1c (HbA1c reduced) was noted in 50 participants overall. Twice as many participants in the intervention groups demonstrated an improvement as compared to the control group (56% of the education group, 51% education plus ACT, and 24% control group.  Conclusions: At 6 months post intervention, HbA1c was reduced in both intervention groups with a greater reduction noted in the nurse-led education intervention

A nurse-led interdisciplinary approach to promote self-management of type 2 diabetes: A process evaluation of post intervention experiences

Rationale, aims and objectives  Self-management of type 2 diabetes through diet, exercise and for many medications, are vital in achieving and maintaining glycaemic control in type 2 diabetes. A number of interventions have been designed to improve self-management, but the outcomes of these are rarely explored from a qualitative angle and even fewer through a process evaluation.  Method  A process evaluation was conducted using a qualitative design with participants randomized to an intervention. Seventy-three people living with type 2 diabetes and hyperglycaemia for a minimum of 1 year, randomized to one of two interventions (n = 34 to an education intervention andn = 39 to an education and acceptance and commitment therapy intervention) completed stage one of the process evaluation, immediately following the intervention through written feedback guided by open-ended questions. A purposive sample of 27 participants completed semi-structured interviews at 3 and 6 months post intervention. Interview data were transcribed and data analysed using a thematic analysis.  Results  The majority of participants described an increase in knowledge around diabetes self-management and an increased sense of personal responsibility. Participants also described changes in self-management activities and reflected on the challenges in instigating and maintaining change to improve diabetes management.  Conclusion  The complexities of implementing change in daily life to improve glycaemic control indicate the need for ongoing support post intervention, which may increase and maintain the effectiveness of the intervention

Discovery of a series of 2-(pyridinyl) pyrimidines as potent antagonists of GPR40

A series of 2-(pyridinyl)pyrimidines were identified as potent GPR40 antagonists. Despite significant challenges related to improving the combination of potency and lipophilicity within the series, the compounds were optimised to identify a suitable in vivo probe compound, which was confirmed to exhibit pharmacology consistent with GPR40 antagonism

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)