Use of the socio-ecological model to explore factors that influence the implementation of a diabetes structured education programme (EXTEND project) inLilongwe, Malawi and Maputo, Mozambique: a qualitative study.

BACKGROUND: Diabetes Self-Management Education and Support (DSMES) programmes are vital for type 2 diabetes mellitus (T2DM) management. However, they are limited in Sub-Saharan Africa (SSA). To address this gap, a DSMES, namedEXTEND was developed in Lilongwe (Malawi) and Maputo (Mozambique). This qualitative study aimed to explore factors that influence the implementation of DSMES in these settings. METHODS: The Socio-ecological model was applied to explore factors influencing the implementation of DSMES in SSA. Data was analysed using the Framework method and constant comparative techniques. Sixty-six people participated in the study: people with T2DM who participated in the EXTEND programme; healthcare professionals (HCPs), EXTEND educators, EXTEND trainers, and stakeholders. RESULTS: Our findings indicate that there is a need to develop an integrated and dedicated diabetes services in SSA healthcare systems, incorporating culturally adapted DSMES and tailored diabetes training to all professions involved in diabetes management. Traditional media and the involvement of community leaders were proposed as important elements to help engage and promote DSMES programmes in local communities. During the design and implementation of DSMES, it is important to consider individual and societal barriers to self-care. CONCLUSION: Findings from this study suggest that multi-faceted factors play a significant role to the implementation of DSMES programmes in LICs. In the future, EXTEND could be incorporated in the development of diabetes training and dedicated diabetes services in SSA healthcare systems, acting as an educational tool for both people with T2DM and HCPs. This project was supported by the Medical Research Council GCRF NCDs Foundation Awards 2016 Development Pathway Funding.

Device-measured physical activity and its association with physical function in adults with type 2 diabetes mellitus.

AIM: To quantify how differences in metrics characterizing physical activity and sedentary behaviour in type 2 diabetes are associated with physical function. METHODS: This analysis included participants' data from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) cross-sectional study. Data were stratified into two groups according to their short physical performance battery (SPPB) score (impaired physical function = SPPB < 10 and normal physical function = SPPB ≥ 10). Hand-grip strength, sit-to-stand 60 (STS-60) and the Duke Activity Status Index (DASI) score were used to assess functional capacity, while physical activity metrics were measured with a wrist-worn accelerometer. The associations between physical activity metrics and measures of functional capacity were analysed using generalized linear modelling. RESULTS: Some 635 adults (median age 66 years, 34% female) were included in this analysis. Overall, 29% of the cohort scored < 10 in the SPPB test indicating impaired physical function. This group spent more time in prolonged sedentary behaviour (600.7 vs. 572.5 min) and undertook less-intense physical activity. Each sd increase in physical activity volume and intensity gradients for those with impaired physical function was associated with 17% more repetitions for STS-60 with similar associations seen for DASI score. Each sd in sedentary time was associated with 15% fewer repetitions in STS-60 and 16% lower DASI score in those with impaired physical function, whereas in normal physical function group it was 2% and 1%, respectively. CONCLUSIONS: The strength of the associations for physical activity measures and functional capacity were modified by physical function status, with the strongest association seen in those with impaired physical function.

Sleep duration, obesity and insulin resistance in a multi-ethnic UK population at high risk of diabetes.

AIMS: Investigating the association between sleep duration, obesity, adipokines and insulin resistance (via Leptin:Adiponectin ratio (LAR)), in those at high risk of type 2 diabetes mellitus (T2DM). METHODS: Adults with impaired glucose regulation (IGR) were included. Fasting bloods for inflammatory biomarkers and glycaemic status, 2-h glucose, anthropometrics, objective physical activity, and self-reported sleep were collected. The average number of hours slept in a 24 h period was categorised as ≤5.5, 6-6.5, 7-7.5, 8-8.5, and ≥9 h. Regression models were fitted with sleep (linear and quadratic) and logistic regression used for IGR and adjusted for age, sex, ethnicity, body mass index, waist circumference and objective physical activity. RESULTS: 2848 participants included (593 with inflammatory marker data). Short sleep and long sleep duration were significantly independently associated with higher body mass index (P < 0.001), body weight (P < 0.01), and waist circumference (P < 0.001). 6-7 h of sleep/24 h is associated with the lowest obesity measures. Fasting insulin and LAR were positively associated with sleep duration. Adiponectin levels were negatively associated with sleep duration. CONCLUSIONS: These results support the evidence of an association between short and long sleep duration and indices of obesity. We demonstrate an independent relationship between long sleep duration and insulin resistance.

Evaluating the impact of an enhanced primary care diabetes service on diabetes outcomes: A before-after study.

Diabetes is an ambulatory care-sensitive condition and a high quality primary care or risk factor control can lead to a decrease in the risk of non-elective hospitalisations while ensuring continuity of care with usual primary care teams. AIMS AND METHODS: In this before and after study, eight primary care practices providing a newer enhanced diabetes model of care in Leicester UK, were compared with matched neighbouring practices with comparable demographic features providing a more expensive integrated specialist-community care diabetes service. The primary outcome at twelve months was to demonstrate equivalence in non-elective bed days. The enhanced practices had primary care physicians and nurses with an interest in diabetes who attended monthly diabetes education meetings and provided care plans and audits. The control practices provided an integrated primary-specialist care service. RESULTS: The difference between the mean change in the non-elective bed days from baseline and at follow up in core and enhanced practices was not statistically significant (mean=2.20 per 100 patients, 95% CI=-0.92 to 5.31 per 100 patients, p=0.14). The analogous change for first outpatients' attendance were 0.23 per 100 patients (95% CI=-0.47 to 0.52 per 100 patients p=0.92) and for diabetes related complications admissions was 0.30 per 100 patients (95% CI=-0.85 to 1.45 per 100 patients p=0.55). CONCLUSION: A model of enhanced primary care based diabetes care appears unlikely to increase hospitalisations, outpatients' attendance or admissions for diabetes related complications.

Assessment of response rates and yields for Two opportunistic Tools for Early detection of Non-diabetic hyperglycaemia and Diabetes (ATTEND). A randomised controlled trial and cost-effectiveness analysis.

AIMS: To assess the opportunistic use in primary care of a computer risk score versus a self-assessment risk score for undiagnosed type 2 diabetes. METHODS: We conducted a randomised controlled trial in 11 primary care practices in the UK. 577 patients aged 40-75years with no current diagnosis of type 2 diabetes were recruited to a computer based risk score (Leicester Practice Computer Risk Score (LPCRS)) or a patient self-assessment score (Leicester Self-Assessment Score (LSAS)). RESULTS: The rate of self-referral blood tests was significantly higher for the LPCRS compared to the LSAS, 118.98 (95% CI: 102.85, 137.64) per 1000 high-risk patient years of follow-up compared to 92.14 (95% CI: 78.25, 108.49), p=0.022. Combined rate of diagnosis of type 2 diabetes and those at risk of developing the disease (i.e. impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)) was similar between the two arms, 15.12 (95% CI: 9.11, 25.08) per 1000 high-risk patient years for LPCRS compared to 14.72 (95% CI: 9.59, 22.57) for the LSAS, p=0.699. For the base case scenario the cost per new case of type 2 diabetes diagnosed was lower for the LPCRS compared to the LSAS, £168 (95% Credible Interval (CrI): 76, 364), and £352 (95% CrI: 109, 1148), respectively. CONCLUSIONS: Compared to a self-assessment risk score, a computer based risk score resulted in greater attendance to an initial blood test and is potentially more cost-effective.

Rationale and design of the randomised controlled trial to assess the impact of liraglutide on cardiac function and structure in young adults with type 2 diabetes (the LYDIA study).

BACKGROUND: The prevalence of type 2 diabetes (T2DM) in younger adults is growing. Compared to the late onset T2DM, it is well recognized that the disease tends to behave more aggressively in the younger age group with evidence of premature micro and macrovasular diseases and shorter life span. This increased mortality is largely attributed to cardiovascular complications. In a recent pilot study, young adults with T2DM were found to have significantly lower peak diastolic strain rate (PEDSR) on cardiac MRI (CMR), a forerunner of diabetic cardiomyopathy. Liraglutide, a glucagon like peptide-1 (GLP-1) analogue, is one of the new classes of glucose lowering therapies licensed to be used in management of T2DM. In randomised controlled trials, liraglutide improves glycaemic control by 1-1.5 % with an added benefit of weight loss of 2-3 kg. In addition, there is emerging evidence elucidating the cardioprotective effects of GLP-1 analogues independent of glycaemic control. In a small study, liraglutide has also been shown to improve cardiac function in patients with coronary ischaemia or congestive heart failure. METHODS AND AIMS: This is a prospective, randomised, open-label, blind end-point (PROBE) active-comparator trial. A total of 90 obese eligible participants with T2DM (18-50 years) will be randomised to either liraglutide 1.8 mg once daily or sitagliptin 100 mg once daily for 26 weeks. The primary aim is to assess whether liraglutide improves diastolic function compared to sitagliptin as measured by PEDSR using CMR. DISCUSSION: Although newer classes of GLP-1 analogues are made available in recent years, there are very few published studies demonstrating the beneficial effect of GLP-1 analogues on cardiovascular endpoints. In a recently published LEADER study, liraglutide has shown superiority to placebo in a population of type 2 diabetes with high risk of cardiovascular disease. To the best of our knowledge, there are no published studies establishing the effect of liraglutide on cardiac function in younger patients with T2DM on a larger scale. The LYDIA study will comprehensively describe changes in various parameters of cardiac structure and function in patients treated with liraglutide aiming to provide new evidence on effect of liraglutide on diastolic function in young obese people with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT02043054.

Guidelines for managing diabetes in Ramadan.

BACKGROUND: Globally there are approximately 90 million Muslims with diabetes of which approximately 400 000 reside within the UK. The holy month of Ramadan is a fundamental practice of this religion of which fasting from sun-rise to sun-set is an integral part. This poses many potential risks for those with diabetes who wish to observe Ramadan. METHODS: The evidence base for best clinical management of Type 1 and Type 2 diabetes during Ramadan was reviewed. We reviewed current and previous recommendations for safe fasting during Ramadan. RESULTS: The risks associated with fasting in those with diabetes and preparing your patient for Ramadan are discussed. We have reviewed the evidence around diet-controlled diabetes and therapies including; metformin, acarbose, metglitinides, sulfonylureas, thiazolidinidiones, dipeptidyl peptidase-4 inhibitor (DPP-4), sodium glucose co-transporter -2 (SGLT-2) inhibitors, glucagon-like peptide -1 (GLP-1) receptor agonists and insulin. CONCLUSION: Up to date guidelines for the management of treatment regimes are set-out for those with Type 1 and Type 2 diabetes who wish to fast during Ramadan.

Safety and effectiveness of non-insulin glucose-lowering agents in the treatment of people with type 2 diabetes who observe Ramadan: a systematic review and meta-analysis.

AIM: To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were included. Data were pooled using random effects models. RESULTS: A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48, 95% confidence interval (CI) 0.36, 0.64; p > 0.0001]. This was not replicated in the RCTs of vildagliptin, but a significant reduction was found in the observational studies (RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high heterogeneity (I(2) = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (-1.81 kg, 95% CI -2.91, -0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001). CONCLUSIONS: The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines.

A randomized controlled trial comparing the GLP-1 receptor agonist liraglutide to a sulphonylurea as add on to metformin in patients with established type 2 diabetes during Ramadan: the Treat 4 Ramadan Trial.

AIMS: To compare a sulphonylurea with the glucagon like peptide-1 (GLP-1) receptor agonist liraglutide in combination with metformin in patients on mono/dual oral therapy with established type 2 diabetes fasting during Ramadan. METHODS: Ninety-nine adults intending to fast during Ramadan [50% male, mean age 52 years, body mass index (BMI) 32 kg/m(2)] were randomized from two UK sites. Baseline data were collected ≥14 days prior to Ramadan and at 3 and 12 weeks after Ramadan. RESULTS: At 12 weeks, more patients in the liraglutide compared with the sulphonylurea group achieved a composite endpoint of haemoglobin A1c (HbA1c) < 7%, no weight gain and no severe hypoglycaemia but this did not reach statistical significance [odds ratio (OR) 4.08, 95% confidence interval (CI) 0.97, 17.22, p = 0.06]. From a baseline of 7.7% there was no change in HbA1c at 12 weeks in the sulphonylurea (+0.02%) compared with a 0.3% reduction in the liraglutide group (adjusted coefficient -0.41, 95% CI -0.83, 0.01, p = 0.05). Significant reductions were also observed in weight and diastolic blood pressure (BP) in the liraglutide compared with the sulphonylurea group. Treatment satisfaction was comparable across the treatment groups. There were no episodes of severe hypoglycaemia in either group, however, self-recorded episodes of blood glucose ≤3.9 mmol/l were significantly lower with liraglutide (incidence rate ratio 0.29, 95% CI 0.19, 0.41, p < 0.0001). CONCLUSIONS: Liraglutide compared with sulphonylurea is well tolerated and maybe an effective therapy in combination with metformin during Ramadan with more patients able to achieve target HbA1c, lose or maintain weight with no severe hypoglycaemia. This was achieved with a high level of treatment satisfaction.

Investigating endothelial activation and oxidative stress in relation to glycaemic control in a multiethnic population.

AIM: An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA) and White Europeans (WE) residing in the UK. METHODS: 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1α and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively. RESULTS: 2,3-Dinor-8-iso-prostaglandin-F1α levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79) versus 8.46 (7.71, 9.29), P = 0.021) after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (ß = 1.08, 95% CI:1.02, 1.14, P = 0.009), fasting (ß = 1.06, 95% CI: 1.02, 1.10, P = 0.002), and 2 hr glucose (ß = 1.02, 95% CI: 1.00, 1.04, P = 0.052). In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P < 0.001). No ethnic differences in ICAM-1 were observed. CONCLUSION: These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.

Stories at the hour of our death.

Storytelling through reminiscence and life review can be an important activity for individuals who are dying. Benefits include catharsis, integration, meaning-making, and the enhancement of relationships. Specific tools for facilitating life stories--taped autobiographies, journals, "reminiscentia," and scrapbooks--are discussed.

Molecular cloning and functional expression of a third isoform of the human calcitonin receptor and partial characterization of the calcitonin receptor gene.

We have cloned and expressed two isoforms of the human calcitonin (hCT) receptor. Primers designed from the published sequence of a CT receptor cloned from an ovarian small cell carcinoma line were used for the polymerase chain reaction amplification of related products from human breast carcinoma MCF-7 cells. Two complementary DNAs were isolated. One clone lacks a 16-amino acid insert in the first intracellular loop and is virtually identical to the receptor recently cloned from the T47D human breast carcinoma cell line. The second clone is another splice variant lacking both the 16-amino acid insert in the first intracellular domain as well as the first 47 amino acids of the amino-terminus extracellular domain. COS-7 cells transfected with either receptor isoform bound [125I]salmon CT with high affinity and responded to hCT with increases in cAMP. Tissue distribution studies revealed the truncated extracellular domain 1 isoform transcripts in human skeletal muscle, kidney, brain, and lung. Analysis of a hCT receptor genomic clone demonstrated an exon/intron organization similar to that of the porcine CT receptor gene, except for a distinct exon coding for the alternatively spliced insert in the first intracellular domain.

Molecular cloning of two receptors from rat brain with high affinity for salmon calcitonin.

Two receptors with high affinity for salmon calcitonin were cloned from the nucleus accumbens region of rat brain. The deduced 479 amino acid sequence of cDNA clone L2175-D20 (designated C1a receptor) is 78% and 66% identical with those reported for human and porcine calcitonin receptors, respectively. Clone U3237-A2 codes for a receptor (designated C1b) that is identical to C1a except for a 37 amino acid insert in the second extracellular domain. COS-7 cells transfected with either transcript bound [125I]salmon calcitonin with high affinity (Kd = 8 pM for C1a; Kd = 48 pM for C1b) and responded to salmon calcitonin with increases in cAMP. Tissue distribution studies revealed C1a transcript in rat brain, skeletal muscle, kidney and lung, whereas C1b was predominantly found in brain.

A comparison of once-daily atenolol and metoprolol using office and ambulatory blood pressure monitoring.

The authors compared the relative safety and efficacy of changing treatment from once-daily atenolol to metoprolol in patients with essential hypertension. A parallel-group randomized clinical trial was conducted in two phases: a 4-week baseline single-blind phase using atenolol 50 mg, followed by a 4-week randomized double-blind treatment phase using either atenolol 50 mg or metoprolol 100 mg administered once daily at noontime. Patients with well-controlled hypertension already prescribed 50 mg of atenolol (with or without the addition of a diuretic) for control of hypertension were selected for participation from the outpatient hypertension clinic of the Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania. Seated blood pressure (BP) and pulse were obtained during the baseline phase and during the randomized treatment phase. Twenty-four-hour ambulatory BP monitoring was performed once during the baseline phase and once during the randomized treatment phase, near the end of each 4-week period. There were no within- and between-treatment differences in office systolic and diastolic BP. There was a slight increase in pulse (average = 5.2 beats/minute; P = .02) for those participants treated with metoprolol. For within-treatment groups, the ambulatory BP data showed no significant differences in systolic and diastolic BPs, except for an increase in morning diastolic BP for those randomized to metoprolol (average = 6.2 mm Hg; P = .01). For between-treatment groups, the metoprolol arm had a higher morning systolic BP (P = .01), a higher morning diastolic BP (P = .03), and a higher nighttime heart rate (P = .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Telling the story: ethics and dying.

What does the telling of stories have to do with theology or religion or ethics? Transcending utilitarian, principlist, or situationist approaches to ethics, one may look at life as story and the way a life is lived as character. "Death is the final chapter in each life story. . . . At death individuals make the ultimate decision, the final choice. . . ." Will they be able to affirm their years of living? Character will determine an individual's responses.