Distress and Living with Diabetes: Defining Characteristics Through an Online Survey.

INTRODUCTION: There is considerable evidence for diabetes reducing quality of life. The impact of such a diagnosis on mental health is less well understood and was subsequently explored here. METHODS: Online PHQ-9 scores (which calculate the severity of depression), Diabetes Distress Screening Scale (DDSS) and EQ-5D-5L (quality-of-life) questionnaires were completed by patients with diabetes, followed by the extraction of data where possible from responders' clinical records. RESULTS: A total of 133 people submitted questionnaires. However, not all data items could be completed by each patient; 35% (45/130) had type I diabetes mellitus (T1DM); 55% (64/117) were women. The overall median age of 117 responders was 60 (IQR 50-68 years). The median aggregated response scores were: EQ-5D-5L 0.74 (IQR 0.64-0.85) (lower quality of life than UK population median of 0.83), DDSS 1.9 (IQR1.3-2.7) (≥ 2 indicates moderate distress) and PHQ-9 5 (IQR2-11) (≥ 5 indicates depression). Higher diabetes distress (DDSS)/lower quality of life EQ-5D-5L/higher depressive symptoms (PHQ-9) linked to female sex (DDSS 0.5/25% above median), younger age (< 50 years DDSS 0.7/35% above median), fewer years after diagnosis (< 10 years DDSS 0.8/40% above median), and obesity (BMI > 35 DDSS 0.6/30% above median). Additionally, a HbA1c reading of ≤ 48 mmol/mol was associated with higher DDSS scores, as did a reduction of more than 5 mmol/mol in HbA1c over the last three HbA1c measurements. The 30 individuals with a history of prescribed antidepressant medication also showed higher diabetes distress scores (DDSS 0.9, equating to 45% above the median). The DDSS score elevation came from an increase in emotional burden and regimen-related distress. DDSS scores were not significantly linked to diabetes type, insulin use, absolute level/change in blood glucose HbA1c. Physician-related distress showed a similar pattern. CONCLUSIONS: A low level of stress in relation to diabetes management may be associated with lower HbA1c. The larger impact of diabetes on mental health in younger women/people with shorter diabetes duration should be noted when considering psychosocial intervention/behavior change messaging. Physician-related distress is a potentially remediable factor. However, this sample was self-selecting, limiting generalization to other samples.

The experience of blood glucose monitoring in people with type 2 diabetes mellitus (T2DM).

BACKGROUND: Finger prick blood glucose (BG) monitoring remains a mainstay of management in people with type 2 diabetes (T2DM) who take sulphonylurea (SU) drugs or insulin. We recently examined patient experience of BG monitoring in people with type 1 diabetes (T1DM). There has not been any recent comprehensive assessment of the performance of BG monitoring strips or the patient experience of BG strips in people with T2DM in the UK. METHODS: An online self-reported questionnaire containing 44 questions, prepared following consultation with clinicians and patients, was circulated to people with T2DM. 186 responders provided completed responses (25.5% return rate). Fixed responses were coded numerically (eg not confident = 0 fairly confident = 1). RESULTS: Of responders, 84% were treated with insulin in addition to other agents. 75% reported having had an HbA1c check in the previous 6 months. For those with reported HbA1c ≥ 65 mmol/mol, a majority of people (70%) were concerned or really concerned about the shorter term consequences of running a high HbA1c This contrasted with those who did not know their recent HbA1c, of whom only 33% were concerned/really concerned and those with HbA1c <65 mmol/mol of whom 35% were concerned. Regarding BG monitoring/insulin adjustment, only 25% of responders reported having sufficient information with 13% believing that the accuracy and precision of their BG metre was being independently checked. Only 9% recalled discussing BG metre accuracy when their latest metre was provided and only 7% were aware of the International Standardisation Organisation (ISO) standards for BG metres. 77% did not recall discussing BG metre performance with a healthcare professional. CONCLUSION: The group surveyed comprised engaged people with T2DM but even within this group there was significant variation in (a) awareness of shorter term risks, (b) confidence in their ability to implement appropriate insulin dosage (c) awareness of the limitations of BG monitoring technology. There is clearly an area where changes in education/support would benefit many.

Satisfaction with a digitally-enabled telephone health coaching intervention for people with non-diabetic hyperglycaemia.

International evidence shows that lifestyle interventions can effectively reduce the risk of developing diabetes in people with non-diabetic hyperglycaemia (NDH). A candidate intervention that has potential to be rolled out at population level is health coaching. Digital interventions offer the means to potentially enhance user satisfaction with health coaching and improve efficiencies. We used a randomised controlled trial to test whether a digitally-enabled health coaching intervention that included an online dashboard and telephone health coaching improved user satisfaction and cost-efficiencies compared with a telephone only health coaching intervention. The primary outcome was satisfaction measured by Client Satisfaction Questionnaire (CSQ-8). 103 participants with NDH were allocated to the telephone coaching only intervention and 106 participants with NDH were allocated to the digital and telephone coaching intervention. In an intention-to-treat analysis satisfaction was higher in participants allocated to the digital and telephone coaching intervention than those allocated to the telephone only intervention, but the difference was not significant. There were no significant differences between the groups on secondary outcomes (HbA1c, BMI, activation, depression, self-management, health status). From a service commissioning perspective the mean incremental cost of the digitally-enabled intervention was £236 ($332; €270). Call times, including administration, were longer for participants allocated to the digitally-enabled intervention. The results show that user satisfaction with digitally-enabled intervention is broadly equivalent with that of telephone delivered interventions in the context of routinely delivered diabetes prevention programmes. There is scope for future work that assesses how economies of scale can be achieved at larger user bases.

Comparison of active treatments for impaired glucose regulation: a Salford Royal Foundation Trust and Hitachi collaboration (CATFISH): study protocol for a randomized controlled trial.

BACKGROUND: Diabetes is highly prevalent and contributes to significant morbidity and mortality worldwide. Behaviour change interventions that target health and lifestyle factors associated with the onset of diabetes can delay progression to diabetes, but many approaches rely on intensive one-to-one contact by specialists. Health coaching is an approach based on motivational interviewing that can potentially deliver behaviour change interventions by non-specialists at a larger scale. This trial protocol describes a randomized controlled trial (CATFISH) that tests whether a web-enhanced telephone health coaching intervention (IGR3) is more acceptable and efficient than a telephone-only health coaching intervention (IGR2) for people with prediabetes (impaired glucose regulation). METHODS: CATFISH is a two-parallel group, single-centre individually randomized controlled trial. Eligible participants are patients aged ≥18 years with impaired glucose regulation (HbA1c concentration between 42 and 47 mmol/mol), have access to a telephone and home internet and have been referred to an existing telephone health coaching service at Salford Royal NHS Foundation Trust, Salford, UK. Participants who give written informed consent will be randomized remotely (via a clinical trials unit) to either the existing pathway (IGR2) or the new web-enhanced pathway (IGR3) for 9 months. The primary outcome measure is patient acceptability at 9 months, determined using the Client Satisfaction Questionnaire. Secondary outcome measures at 9 months are: cost of delivery of IGR2 and IGR3, mental health, quality of life, patient activation, self-management, weight (kg), HbA1c concentration, and body mass index. All outcome measures will be analyzed on an intention-to-treat basis. A qualitative process evaluation will explore the experiences of participants and providers with a focus on understanding usability of interventions, mechanisms of behaviour change, and impact of context on delivery and user acceptability. Qualitative data will be analyzed using Framework. DISCUSSION: The CATFISH trial will provide a pragmatic assessment of whether a web-based information technology platform can enhance acceptability of a telephone health coaching intervention for people with prediabetes. The data will prove critical in understanding the role of web applications to improve engagement with evidence-based approaches to preventing diabetes. TRIAL REGISTRATION: ISRCTN16534814 . Registered on 7 February 2016.

Dapagliflozin: a review on efficacy, clinical effectiveness and safety.

INTRODUCTION: The prevalence of type 2 diabetes mellitus has reached epidemic proportions. Progressive deterioration in glycaemic control and the current limitations of existing therapies such as weight gain and hypoglycaemia led us to welcome the first of a new class of drugs. Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a novel mode of therapy independent of insulin secretion or action. By blocking glucose reabsorption in the kidney they lead to an increase in urinary glucose excretion with reduction in plasma glucose levels. AREAS COVERED: In this article, we will review inhibition of SGLT2 as a novel strategy for the treatment of type 2 diabetes mellitus with dapagliflozin . PubMed and MEDLINE were searched for literature published up to July 2012, for efficacy, clinical effectiveness and safety reports of dapagliflozin. EXPERT OPINION: Improvement in glycaemic control with a low risk of hypoglycaemia, concomitant weight loss and the potential of lowering of blood pressure make SGLT2 inhibition an attractive approach using dapagliflozin therapy. Many SGLT2 inhibitors are undergoing Phase III clinical trials and more are in Phase I and II clinical trials.

Real time presence of a microbiologist in a multidisciplinary diabetes foot clinic.

Multidisciplinary foot-care teams (MDFT) are recommended in the management of severe diabetic foot disease [1]. However, even though infection is often the dominant immediate risk, it is rare to have real time input from a microbiologist. We highlight the value of a microbiologist as a MDFT member.

Early diagnosis of acromegaly: computers vs clinicians.

BACKGROUND: Early diagnosis of a number of endocrine diseases is theoretically possible by the examination of facial photographs. One of these is acromegaly. If acromegaly were found, early in the course of the disease, morbidity would be lessened and cures more likely. OBJECTIVES, DESIGN, PATIENTS, MEASUREMENTS: Our objective was to develop a computer program which would separate 24 facial photographs, of patients with acromegaly, from those of 25 normal subjects. The key to doing this was to use a previously developed database that consisted of three-dimensional representations of 200 normal person's heads (SIGGRAPH '99 Conference Proceedings, 1999). We transformed our 49, two-dimensional photos into three-dimensional constructs and then, using the computer program, attempted to separate them into those with and without the features of acromegaly. We compared the accuracy of the computer to that of 10 generalist physicians. A second objective was to examine, by a subjective analysis, the features of acromegaly in the normal subjects of our photographic database. RESULTS: The accuracy of the computer model was 86%; the average of the 10 physicians was 26%. The worst individual physician, 16%, the best, 90%. The faces of 200 normal subjects, the original faces in the database, could be divided into four groups, averaged by computer, from those with fewer to those with more features of acromegaly. CONCLUSIONS: The present computer model can sort photographs of patients with acromegaly from photographs of normal subjects and is much more accurate than the sorting by practicing generalists. Even normal subjects have some of the features of acromegaly. Screening with this approach can be improved with automation of the procedure, software development and the identification of target populations in which the prevalence of acromegaly may be increased over that in the general population.

Eutrophic remodeling of small arteries in type 1 diabetes mellitus is enabled by metabolic control: a 10-year follow-up study.

Type 2 diabetes mellitus profoundly changes small artery remodeling in response to hypertension. Abnormal increases of both wall thickness and lumen diameter are associated with an increased mortality. Changes to small artery structure in response to blood pressure (BP) in patients with type 1 diabetes mellitus have never been examined. In 1997, 17 patients with type 1 diabetes mellitus and 9 control subjects underwent in vitro assessment of gluteal-fat small arteries using pressure myography. Patients with BP <140/90 mm Hg (systolic BP: 119+/-3 mm Hg; n=12) had normal-resistance artery structure. However, patients with BP >140/90 mm Hg (systolic BP: 152+/-5 mm Hg; n=5) demonstrated vascular hypertrophic remodeling with a significant increase in the medial cross-sectional area and wall thickness. In 2008, 8 of the original 17 diabetic patients returned for a repeat assessment. All 8 of the patients had significantly improved cholesterol (2008: 154+/-9 mg/dL versus 1997: 191+/-9 mg/dL; P=0.01) and low-density lipoprotein cholesterol (2008: 79+/-8 mg/dL versus 1997: 122+/-9 mg/dL; P=0.003) but higher BPs (systolic BP: 2008: 136+/-3 mm Hg versus 1997: 119+/-6 mm Hg; P=0.03). Glycemia was improved (2008: 7.9+/-0.3% versus 1997: 8.9+/-0.6%; P=0.17), but not significantly so. In the small arteries studied, there were significant increases in medial wall thickness and wall:lumen ratio, but cross-sectional area was unchanged, indicating eutrophic remodeling. Collectively, these findings suggest that, with poor metabolic control, small arteries from patients with type 1 diabetes mellitus show hypertrophic growth in response to elevated BP, similar to that seen in type 2 diabetes mellitus. However, metabolic improvements enable eutrophic remodeling to occur in response to an increase in BP. This has only been observed previously in patients without diabetes mellitus.

Small vessel remodeling and impaired endothelial-dependent dilatation in subcutaneous resistance arteries from patients with acromegaly.

CONTEXT: Patients with acromegaly have increased morbidity and mortality, predominantly from cardiovascular disease. Hypertension and diabetes are more prevalent, and both cause small vessel remodeling and endothelial dysfunction. OBJECTIVE: To understand the structure and function of small arteries in acromegaly, sc blood vessels from gluteal fat biopsies were harvested from 18 patients with active disease (AD; age, 56 +/- 15 yr; 14 males), 23 patients in remission (CD; age, 55 +/- 12 yr; 15 males), and 20 healthy controls (age, 55 +/- 11 yr; 10 males) and examined in vitro using pressure myography. DESIGN: Contractile responses to cumulative noradrenaline concentrations were recorded and followed by dose-dependent dilator responses to acetylcholine. The acetylcholine protocol was repeated after incubation with a nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester) and cyclooxygenase inhibitor (indomethacin). After perfusion with Ca(2+)-free physiological saline solution, structural measurements were recorded at varying intraluminal pressures (3-180 mm Hg). RESULTS: Wall thickness and wall:lumen ratio were increased in AD, reduced with treatment but remained greater in CD than controls. Wall cross-sectional area was increased in AD vs. controls (P < 0.001), decreased with treatment (AD vs. CD, P < 0.001), but remained higher than controls (CD vs. controls, P = 0.015). Growth index was increased in AD (20%) compared to controls (CD, 9%). Contractility was similar in all groups. Endothelial-dependent dysfunction was evident in AD compared with CD (P < 0.001) and controls (P < 0.01). Dilation did not change after N-nitro-L-arginine methyl ester but was impaired after indomethacin incubation. CONCLUSION: Active acromegaly is associated with hypertrophic remodeling of the vascular wall and embarrassed endothelial function due to reduced nitric oxide and endothelium-derived hyperpolarizing factor bioavailability, both of which may contribute to the early mortality from cardiovascular disease.

Treatment of acromegaly improves quality of life, measured by AcroQol.

BACKGROUND: AcroQol is a disease-generated questionnaire, developed to assess quality of life (QOL) in patients with acromegaly. We have previously demonstrated severely impaired QOL in patients with acromegaly and the value of AcroQol in measuring QOL in a cross-sectional study compared with the non-disease-specific generic tools 'Psychological general wellbeing schedule' (PGWBS) and EuroQol (EQ-5D), and the disease-specific signs and symptoms score (SSS). AIM, SUBJECTS AND METHODS: We re-evaluated these tools in a longitudinal study of 56 of the previously reported patients (33 male, mean age 55 +/- 15 years), in order to determine change in QOL over time and the effect of different treatment modalities. Data were analysed using Spearman's correlation tests. RESULTS: Baseline median IGF-I was 354 ng/ml (range 48-899) and at re-evaluation 217 ng/ml (60-594) (P < 0.001) [median time interval 608 days (113-1136)]. Analysis of change in IGF-I levels and AcroQol scores demonstrated a significant negative correlation (i.e. a reduction in IGF-I being associated with improved overall QOL (r = -0.36, P = 0.006). Significant negative correlations were also seen in the physical (r = -0.33, P = 0.01), psychological (r = -0.37, P = 0.005) and appearance (r = -0.42, P = 0.001) AcroQol subdomains. No correlations were seen between change in IGF-I and change in overall PGWBS score or subdomains, SSS or EQ-5D. CONCLUSIONS: In summary, of the tools studied we have demonstrated AcroQol to be uniquely capable of detecting changes in QOL associated with treatment-induced improvement in the main biochemical marker of disease activity in patients with acromegaly. Further studies are required to evaluate the long-term biological significance of the changes seen in AcroQol.

Recent developments in the therapy of acromegaly.

Acromegaly, a condition due to growth hormone hypersecretion usually from a benign pituitary tumour, is associated with significant morbidity and mortality. Disease control leads to normalisation of life expectancy with a reduction in signs and symptoms. Treatment modalities include surgery, radiotherapy and medical management. Surgery is the primary treatment in most of the patients, with success rates of 61-91% reported for those with microadenomas who are operated on by a specialist pituitary surgeon; however, most patients have macroadenomas and, although benefiting from surgery, are not cured and require additional medical therapy. This review will focus on emerging concepts in the medical treatment of acromegaly.

Detecting acromegaly: screening for disease with a morphable model.

Acromegaly is a rare disorder which affects about 50 of every million people. The disease typically causes swelling of the hands, feet, and face, and eventually permanent changes to areas such as the jaw, brow ridge, and cheek bones. The disease is often missed by physicians and progresses beyond where it might if it were identified and treated earlier. We consider a semi-automated approach to detecting acromegaly, using a novel combination of support vector machines (SVMs) and a morphable model. Our training set consists of 24 frontal photographs of acromegalic patients and 25 of disease-free subjects. We modelled each subject's face in an analysis-by-synthesis loop using the three-dimensional morphable face model of Blanz and Vetter. The model parameters capture many features of the 3D shape of the subject's head from just a single photograph, and are used directly for classification. We report encouraging results of a classifier built from the training set of real human subjects.

Treatment of pituitary tumors: pegvisomant.

Pegvisomant is a pegylated analog of growth that functions as a growth hormone receptor antagonist. The drug is capable of normalizing serum IGF-I concentrations (the chief mediator of disease activity in acromegaly) in 97% of patients, and therapy is associated with significant improvements in the symptoms and signs of GH excess. Biochemical control may be achieved with pegvisomant in patients wholly or partially resistant to somatostatin analogs, and there are emerging data to suggest that the drug may be particularly suitable for patients with acromegaly and co-existent diabetes mellitus.

The place of pegvisomant in the acromegaly treatment algorithm.

The disfiguring disease acromegaly results from hypersecretion of growth hormone (GH). The main goals of treatment for acromegaly include normalisation of biochemical markers of disease activity to restore normal life expectancy, amelioration of signs and symptoms of the disease, removal of the pituitary tumour without damaging the optic chiasm and other peripituitary structures, and preservation of pituitary function. Conventional options for treatment of acromegaly include surgery, radiotherapy (RT), and medical therapy with either dopamine agonists or somatostatin (SMS) analogues. The advent of the genetically engineered growth hormone analogue pegvisomant is unlikely to alter significantly the place of surgery and RT in the treatment algorithm for acromegaly biochemical control as determined based on serum IGF-I concentrations is achievable with pegvisomant in virtually all patients, and it will clearly become the drug of choice in patients partially or completely unresponsive to SMS analogues. Preliminary studies suggest improved insulin sensitivity for a given IGF-I with pegvisomant compared with SMS analogues; if these results are confirmed by results of future studies, such a metabolic advantage may encourage the use of pegvisomant.

Pegvisomant: a novel pharmacotherapy for the treatment of acromegaly.

Pegvisomant is a pegylated analogue of growth hormone (GH) that functions as a growth hormone receptor antagonist. Clinical trials of its use in acromegaly commenced in 1997; the drug was approved in the US in March 2003 and in Europe in November 2003. In the same year, it was made available on prescription in several European countries, with further launches due in 2004. Pegvisomant is capable of normalising serum insulin-like growth factor-I concentrations (the chief mediator of disease activity in acromegaly) in 97% of patients with active acromegaly, and therapy is associated with a significant improvement in the symptoms and signs of GH excess. Disease control is achievable with pegvisomant in patients who are wholly or partially resistant or do not tolerate somatostatin analogues; preliminary data suggest that the drug may be particularly suitable for patients with acromegaly and co-existent diabetes mellitus.

The challenges of reliance on insulin-like growth factor I in monitoring disease activity in patients with acromegaly.

Serum insulin-like growth factor I (IGF-I) is an important marker of disease activity in patients with acromegaly, and epidemiological data indicate control of circulating IGF-I in patients with acromegaly restores life expectancy to normal. Improvements in the quality of, and access to, IGF-I assays has encouraged monitoring of acromegaly with IGF-I, although circulating growth hormone (GH) and IGF-I values provide different information, so ideally both should be monitored. However, the introduction of the GH receptor antagonist pegvisomant poses new challenges. Pegvisomant binds with high affinity to GH receptors, thereby blocking the action of GH at the tissue level and rendering the hormone biologically inactive. This leaves IGF-I as the principal marker of disease activity. It is conceptually possible to induce a state of functional GH deficiency (GHD) with pegvisomant with IGF-I values within the normal range. With the goal of minimizing the risk of over-treatment and GHD, we have provided preliminary guidance on the target range for IGF-I in patients receiving pegvisomant based on the gender- and decade-based percentile ranges for IGF-I of adult patients with untreated GHD enrolled in the Pfizer International Metabolic Database (KIMS).