Seamus Sreenan

Once-Weekly Exenatide Versus Once- or Twice-Daily Insulin Detemir Randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas

OBJECTIVE This multicenter, open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin detemir in patients with type 2 diabetes inadequately controlled with metformin (with or without sulfonylureas). RESEARCH DESIGN AND METHODS Patients were randomized to EQW (2 mg) or detemir (once or twice daily, titrated to achieve fasting plasma glucose ≤5.5 mmol/L) for 26 weeks. The primary outcome was proportion of patients achieving A1C ≤7.0% and weight loss ≥1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes included measures of glycemic control, cardiovascular risk factors, and safety and tolerability. RESULTS Of 216 patients (intent-to-treat population), 111 received EQW and 105 received detemir. Overall, 44.1% (95% CI, 34.7–53.9) of EQW-treated patients compared with 11.4% (6.0–19.1) of detemir-treated patients achieved the primary outcome (P < 0.0001). Treatment with EQW resulted in significantly greater reductions than detemir in A1C (least-square mean ± SE, −1.30 ± 0.08% vs. −0.88 ± 0.08%; P < 0.0001) and weight (−2.7 ± 0.3 kg vs. +0.8 ± 0.4 kg; P < 0.0001). Gastrointestinal-related and injection site–related adverse events occurred more frequently with EQW than with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group). CONCLUSIONS Treatment with EQW resulted in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir, with a low risk of hypoglycemia. These results suggest that EQW is a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs.

What’s distressing about having type 1 diabetes? A qualitative study of young adults’ perspectives

BackgroundDiabetes distress is a general term that refers to the emotional burdens, anxieties, frustrations, stressors and worries that stem from managing a severe, complex condition like Type 1 diabetes. To date there has been limited research on diabetes-related distress in younger people with Type 1 diabetes. This qualitative study aimed to identify causes of diabetes distress in a sample of young adults with Type 1 diabetes.MethodsSemi-structured interviews with 35 individuals with Type 1 diabetes (23–30 years of age).ResultsThis study found diabetes related-distress to be common in a sample of young adults with Type 1 diabetes in the second phase of young adulthood (23–30 years of age). Diabetes distress was triggered by multiple factors, the most common of which were: self-consciousness/stigma, day-to-day diabetes management difficulties, having to fight the healthcare system, concerns about the future and apprehension about pregnancy. A number of factors appeared to moderate distress in this group, including having opportunities to talk to healthcare professionals, attending diabetes education programmes and joining peer support groups. Young adults felt that having opportunities to talk to healthcare professionals about diabetes distress should be a component of standard diabetes care.ConclusionsSome aspects of living with diabetes frequently distress young adults with Type 1 diabetes who are in their twenties. Clinicians should facilitate young adults’ attendance at diabetes education programmes, provide them with opportunities to talk about their diabetes-related frustrations and difficulties and, where possible, assist in the development of peer-support networks for young adults with diabetes.

Prevalence of the metabolic syndrome in patients with diabetes mellitus.

BackgroundMetabolic syndrome (MetS) is a vascular risk factor with prevalence in the general population of 17–25%.AimTo determine the prevalence of MetS in patients with diabetes mellitus (DM).MethodsA total of 200 patients [18% type 1 (T1DM), 82% type 2 (T2DM)] attending for annual review were studied. Standard blood tests were requested. Blood pressure and waist circumference were measured. Adult Treatment Panel III (ATP III) criteria for diagnosis of MetS were applied.ResultsA total of 122 (61%) patients had MetS. More patients with T2DM (69.5%) than TIDM (22.2%) had MetS. Despite treatment of DM (100%), hypertension (69.5%) and dyslipidaemia (48.3%), 114 patients (57%) still met the criteria for MetS at time of study.ConclusionsMost T2DM patients have MetS but it is uncommon in T1DM. Despite treatment, almost half of patients still met the criteria for MetS. Aggressive treatment of MetS components is required to reduce cardiovascular risk in DM.

Association between Sleep Disruption and Levels of Lipids in Caucasians with Type 2 Diabetes

Aim. To investigate the association between sleep quality and duration with lipid and glycaemic control in Caucasian subjects with type 2 diabetes. Methods. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in 114 type 2 diabetes (T2DM) subjects. Comparisons were made between subjects with different sleep quality and sleep duration. Hierarchical multiple regression analyses were used to determine contributors to metabolic parameters. Results. Subjects with poor sleep quality (PQ; PSQI ≥ 6) had higher systolic blood pressure, glycated haemoglobin, urine albumin : creatinine ratio (UAC), total cholesterol (TC), and triglycerides (TG) (P < 0.05 for all) compared to those with good sleep quality (GQ; PSQI ≤ 5). Long sleep duration (LSD) subjects had higher TC and short sleep duration (SSD) subjects had higher TG compared to those with medium sleep duration. Sleep duration and PSQI score were independent predictors of TC and low-density lipoprotein cholesterol (LDL), contributing to 14.0% and 6.1% of the total variance, respectively. Conclusions. In this Caucasian T2DM population, PQ is associated with adverse cardiovascular risk markers, and long and short sleep disruptions have an independent negative impact on lipids. Sleep assessment should be included as part of a diabetes clinic review.

Prevalence of anaemia in patients with Diabetes Mellitus

BackgroundAnaemia is an increasingly recognised entity in patients with diabetes mellitus.AimsWe aimed to determine the prevalence of anaemia in our population of patients with diabetes, and to examine the factors associated with anaemia.MethodsThe haemoglobin (Hb) levels in a consecutive series of patients attending for annual review of their diabetes over a three-month period were measured. Patients were classified as anaemic as per the WHO criteria.ResultsDuring the period of study, 270 patients attended for review. Eleven per cent of males and 16% of females were anaemic. Seventy four per cent of anaemic patients had a serum creatinine <110μmol/l and 72% of anaemic patients had a calculated creatinine clearance of >60ml/min.ConclusionsAnaemia was relatively common in patients attending for routine out-patient diabetes clinic review. The high prevalence of anaemia supports the routine screening for anaemia in the diabetes out-patient clinic, including in those without overt nephropathy.

A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin

Abstract Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet‐shaped double‐layered microneedle (MN) arrays with water‐swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet‐shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (˜ 1.6 N cm− 2) with rat skin. By harnessing the MNs reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin‐loaded MN patch released 60% of insulin when immersed in saline over the course of 12 h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self‐adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics. Graphical abstract A bio‐inspired, self‐adherent microneedle (MN) patch is designed for effective transdermal protein drug delivery. The dual‐functional MN patch achieved not only a firm adhesion to live animal skin tissue, but also a prolonged insulin drug delivery following a mild loading process into swellable tips with minimal loss of biofunctionality. This transdermal delivery platform using self‐adherent MN patches can be applied for a variety of protein drugs requiring sustained release kinetics. Figure. No Caption available.

The importance of night-time systolic blood pressure in diabetic patients: Dublin Outcome Study

Objective: Diabetic patients exhibit a higher cardiovascular risk compared to people without diabetes. The use of ambulatory blood pressure monitoring (ABPM) is gaining popularity in this population. Night-time SBP has consistently been shown to be a potent predictor of cardiovascular risk in the normal population. We studied the predictive value of night-time ABPM in a cohort of diabetic patients. Research design and methods: At baseline, when not on antihypertensive medication, 11 291 patients (5326 men, mean age 54.6 years) underwent ABPM. Using a computerized national registry of death, mortality outcome was ascertained. Among 859 diabetic patients with a mean follow-up of 5.3 years, there were 74 deaths. Results: Compared to people without diabetes, those with diabetes had daytime and night-time SBP of 146.4 vs. 145.1 (P = NS) and 131.2 vs. 126.4 mmHg (P < 0.0001), respectively. As a consequence, more diabetic patients had a non-dipping night-time SBP profile (47.4 vs. 35.5%; P =  < 0.0001). In a Cox proportional-hazards model, night-time SBP was an independent predictor of cardiovascular mortality in diabetic patients after adjustment for sex, age, smoking history, previous cardiovascular events, BMI and daytime SBP. The resultant hazard ratio for a 10-mmHg increase in night-time SBP for total cardiovascular, stroke and cardiac mortality was 1.32 (1.12–1.69), 1.95 (1.18–3.20) and 1.24 (0.99–1.56), respectively. Conclusion: Night-time SBP is a significant predictor of cardiovascular mortality in patients with diabetes.

Dealing with the devil: weight loss concerns in young adult women with type 1 diabetes

AIMS AND OBJECTIVES To examine the weight loss concerns of young adults with type 1 diabetes. BACKGROUND Eating disorders are prevalent in young women with type 1 diabetes. DESIGN Qualitative. METHODS Interviews with 35 young adults (23-30 years of age) with type 1 diabetes and 13 healthcare professionals. RESULTS Most female interviewees were concerned about the difficulties of losing weight when having diabetes. Six female interviewees developed severe eating disturbances when they were younger. These women initially regarded their disturbed eating behaviour positively and engaged in weight loss activities intermittently. However, over time, they lost control of their behaviour, and it came to dominate their lives. Family conflict often intensified disordered eating behaviours. Eventually all of these women managed to transition away from their behaviour, although this process took, for some of them, several years. Several of them (now in their early to late twenties), however, continued to struggle with weight loss impulses. Healthcare professionals felt that eating- and weight-related issues often went undiagnosed and undocumented in young adult women with type 1 diabetes. CONCLUSION Many young women with type 1 diabetes are worried about their weight, but will not engage in risky weight loss activities because of concerns about their health. A minority of young adult women will develop more severe eating-related disturbances. These eating disturbances may last a significant amount of time before clinicians become aware of them. These women may also experience disordered weight loss impulses for sometime after clinical interventions. RELEVANCE TO CLINICAL PRACTICE Clinicians should screen young adult women with type 1 diabetes for eating disorders and monitor young adult women who have developed eating disorders over the longer term. There may be a need to provide asymptomatic young women with diabetes with information about the potential risks of insulin omission.

Endothelial Progenitor Cells in Mothers of Low-Birthweight Infants: A Link between Defective Placental Vascularization and Increased Cardiovascular Risk?

CONTEXT Offspring birthweight is inversely associated with future maternal cardiovascular mortality, a relationship that has yet to be fully elucidated. Endothelial progenitor cells (EPCs) are thought to play a key role in vasculogenesis, and EPC numbers reflect cardiovascular risk. OBJECTIVE Our objective was to ascertain whether EPC number or function was reduced in mothers of low-birthweight infants. DESIGN AND SETTING This was a prospective cohort study in a general antenatal department of a university maternity hospital. PARTICIPANTS Twenty-three mothers of small for gestational age (SGA) infants (birthweight < 10th centile) and 23 mothers of appropriate for gestational age (AGA) infants (birthweight ≥ 10th centile) were recruited. MAIN OUTCOME MEASURES Maternal EPC number and function, conventional cardiovascular risk markers, and cord blood adiponectin were measured. RESULTS Median EPC count was lower (294 vs. 367, P = 0.005) and EPC migration was reduced (0.91 vs. 1.59, P < 0.001) in SGA compared with AGA infants, with no difference in EPC adhesion (0.221 vs. 0.284 fluorescence units, P = 0.257). Maternal triglyceride levels were higher in SGA than AGA infants (0.98 vs. 0.78 mmol/liter, P = 0.006), but there was no difference in cholesterol, glucose, insulin, glycosylated hemoglobin, adiponectin, or blood pressure. There was a moderate monotone (increasing) relationship between birthweight and umbilical cord blood adiponectin (r = 0.475, P = 0.005). CONCLUSION Giving birth to an SGA infant was associated with lower maternal EPC number and reduced migratory function. Cord blood adiponectin was significantly correlated with birthweight.

Comparison of performance in a four year graduate entry medical programme and a traditional five/six year programme

BackgroundIn 2006 the Royal College of Surgeons in Ireland, (RCSI), introduced the first four year Graduate Entry Programme (GEP) in medicine in Ireland in line with national policy to broaden access to medical education. One concern considered at the time, was whether the GEP students could be trained to the same standard as their undergraduate Direct Entry Programme (DEP, five/six year duration) counterparts in the shorter time frame. Since students from both cohorts undertake the same examinations in the final two years, it is possible to directly compare GEP vs DEP outcomes. The primary aim of the current study was to analyse the comparative performance of GEP and DEP students undergoing these examinations between 2008 and 2013.MethodsScores from five assessments performed during the final two years were transformed to z scores for each student and 4 scores for the penultimate year were summed to create a unit weighted composite score. The resultant scores for each of the two years were used to assess the comparative performance of GEP vs DEP cohorts and to perform sub-cohort analyses of GEP outcomes.ResultsIn all cohorts/years examined, evidence demonstrated significantly better assessment outcomes for the GEP group for the final two years’ examinations as compared with the DEP group. In all but one cohort examined, this advantage was retained when nationality factors were excluded. Further analyses showed no difference in outcomes between GEP students having science vs. non-science backgrounds and/or between those from EU vs non-EU backgrounds. Finally, data suggested weak correlations between total composite scores and entry scores in American (r = 0.15) and Australian (r = 0.08) medical school admissions tests.ConclusionsWe have shown for the first time in Ireland, that graduate-entry students perform at least as well, or even better, than a corresponding undergraduate-entry group. Moreover, having a scientific background on entry to the GEP confers no advantage in final assessments. These data provide evidence of the viability of the graduate entry route into medical education in Ireland.