Informing and Empowering Patients and Clinicians to Make Evidence-Supported Outcome-Based Decisions in Relation to SGLT2 Inhibitor Therapies: The Use of the Novel Years of Drug administration (YoDa) Concept.

The American Diabetes Association guidelines for the management of type 2 diabetes mellitus recommends treating patients with atherosclerotic cardiovascular diseases, heart failure or diabetic kidney disease with sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists, irrespective of the baseline HbA1c, to reduce adverse renal and cardiovascular outcomes. Initiation of such therapies have a significant cost impact on health economies. Cost of gain in quality-adjusted life-years is normally used for cost effectiveness for a particular drug. In the absence of head-to-head comparisons, prescribers may go for the cheapest option, which may not necessarily be the right decision. We propose using the calculated 'YoDa' (Years of Drug administration) as an easily comparable metric between the drug accrual cost and clinical outcomes. YoDa is calculated as a product of numbers needed to treat and the median duration in years that the trial ran over, to accrue the positive clinical outcomes. Clinical phenotyping of the patient to the specific inclusion and exclusion criteria of relevant clinical trials could guide the clinician to choose the most appropriate therapy. We also propose a series of steps or 'deliberations', which a clinician should consider in making a final choice of sodium-glucose co-transporter-2 inhibitor therapy. A comprehensive summary of the sodium-glucose co-transporter-2 inhibitor trials, clinical phenotyping and YoDa calculations for various significant clinical outcomes could assist making evidence-based, patient-individualised and cost-effective management plans for diabetes care. Informing and Empowering Patients and Clinicians to Make Evidence-Supported Outcome-Based Decisions in Relation to SGLT2 Inhibitor Therapies: The Use of The Novel Years of Drug administration (YoDa) Concept.

Association of hypoglycaemia in screening oral glucose tolerance test in pregnancy with low birth weight fetus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common metabolic derangement in pregnant women. In the women identified to be at high risk of GDM, a 75 g oral glucose tolerance test (OGTT) at 24-28 wk gestation is the recommended screening test in the United Kingdom as per National Institute for Health and Care Excellence (NICE). Hypoglycaemia following the glucose load is often encountered and the implication of this finding for the pregnancy, fetus and clinical care is unclear. AIM: To determine the prevalence of hypoglycaemia at any time during the screening OGTT and explore its association with birth weight. METHODS: All deliveries between 2009 and 2013 at the local maternity unit of the University hospital were reviewed. Of the total number of 24,154 women without pre-existing diabetes, those who had an OGTT for GDM screening based on NICE recommended risk stratification, who had a singleton delivery and had complete clinical and demographic data for analysis, were included for this study (n = 3537). Blood samples for fasting plasma glucose (FPG), 2-hour plasma glucose (2-h PG) and HbA1c had been obtained. Birth weight was categorised as low (≤ 2500 g), normal or Macrosomia (≥ 4500 g) and blood glucose ≤ 3.5 mmol/L was used to define hypoglycaemia. Binary logistic regression was used to determine the association of various independent factors with dichotomized variables; the differences between frequencies/proportions by χ 2 test and comparison between group means was by one-way ANOVA. RESULTS: Amongst the study cohort (3537 deliveries), 96 (2.7%) women had babies with LBW (< 2500 g). Women who delivered a LBW baby had significantly lower FPG (4.3 ± 0.6 mmol/L, P = 0.001). The proportion of women who had a 2-h PG ≤ 3.5 mmol/L in the LBW cohort was significantly higher compared to the cohorts with normal and macrosomic babies (8.3% vs 2.8% vs 4.2%; P = 0.007). The factors which predicted LBW were FPG, Asian ethnicity and 2-h PG ≤ 3.5 mmol/L, whereas maternal age, 2-h PG ≥ 7.8 mmol/L and HbA1c were not significant predictors. CONCLUSION: A low FPG and 2-h PG ≤ 3.5 mmol/L on 75-gram OGTT are significantly associated with low birth weight in women identified as high risk for GDM. Women of ethnic backgrounds (Asians) appear to be more susceptible to this increased risk and may serve as a separate cohort in whom we should offer more intensive follow up and screening for complications. Cost implications and resources for follow up would need to be looked at in further detail to support these findings.

Hyperthyroidism and Graves' disease: Is an ultrasound examination needed?

AIM: The aim of our study was to assess the limitation of clinical examination in determining the morphology of thyroid gland in patients with hyperthyroidism and its implications. METHODS: A retrospective analysis of consecutive patients with hyperthyroidism seen in a tertiary endocrine clinic were analyzed. Sub-analysis was performed on patients with proven Graves' disease. RESULTS: Of the 133 patients included in this study with hyperthyroidism, 60 (45%) patients had significant nodularity on ultrasound (US). However, only 67% of these were identified on clinical examination. In patients with confirmed Graves' disease (n = 73), the discordance between US and clinical examination was very similar (18 of 30 patients, 60%). CONCLUSION: US should form an essential part of the evaluation of hyperthyroidism as the morphology of thyroid gland could be variable and nodules in these glands would also need to be appropriately investigated. This would also significantly influence decision-making and appropriate immediate and follow-up management plan.

The role of cumulative growth hormone exposure in determining mortality and morbidity in acromegaly: a single centre study.

PURPOSE: Acromegaly has traditionally been associated with significant mortality and cardiovascular morbidity. The aim of this study was to assess the overall mortality and improvement in mortality and morbidity in acromegaly and correlate these with cumulative growth hormone exposure. METHODS: All patients treated for acromegaly at our centre until 2012 were analysed in this retrospective observational study. Baseline demographic details such as age at diagnoses, radiological features and pituitary status were obtained on these 167 patients. Cumulative GH levels (GHy) were calculated as a sum of average of GH readings in consecutive years. Mortality rates and development of new diabetes, hypertension and cardiovascular events (stroke, congestive cardiac failure and ischaemic heart disease) were assessed. RESULTS: The SMR for overall cohort was 1.6. There has been a significant improvement in SMR over the past two decades (SMR until 1992 2.5; SMR since 1992 1.0). Cumulative GH exposure was significantly high in patients who died (35.2 vs 24.1, p < 0.01) and in those with incident metabolic or vascular events during follow up (51.6 vs 24.4, p = 0.0001). The cardiovascular event rate of the 'new' cohort was significantly better than the 'old' cohort (8.0 vs. 29.1 %, p < 0.001). CONCLUSION: There has been significant improvement in mortality and morbidity associated with acromegaly, in the setting of routine care in a specialized endocrine unit. Early and effective treatment to 'control' acromegaly could reduce GH exposure and hence vascular comorbidities.

Quality of diabetes care worldwide and feasibility of implementation of the Alphabet Strategy: GAIA project (Global Alphabet Strategy Implementation Audit).

BACKGROUND: The Alphabet Strategy (AS) is a diabetes care checklist ensuring "important, simple things are done right all the time." Current audits of diabetes care in developed countries reveal wide variations in quality with performance of care processes frequently sub-optimal. This study had three components:• an audit to assess diabetes care quality worldwide,• a questionnaire study seeking opinions on the merits of the AS,• a pilot study to assess the practicality of implementation of the AS in a low socioeconomic setting. METHODS: Audit data was collected from 52 centres across 32 countries. Data from 4537 patients were converted to Quality and Outcome Framework (QOF) scores to enable inter-centre comparison. These were compared to each country's Gross Domestic Product (GDP), and Total Health Expenditure percentage per capita (THE%). The opinions of diabetes patients and healthcare professionals from the diabetes care team at each of these centres were sought through a structured questionnaire. A retrospective audit on 100 randomly selected case notes was conducted prior to AS implementation in a diabetes outpatient clinic in India, followed by a prospective audit after four months to assess its impact on care quality. RESULTS: QOF scores showed wide variation across the centres (mean 49.0, range 10.2-90.1). Although there was a positive relationship between GDP and THE% to QOF scores, there were exceptions. 91% of healthcare professionals felt the AS approach was practical. Patients found the checklist to be a useful education tool. Significant improvements in several aspects of care as well as 36% improvement in QOF score were seen following implementation. CONCLUSIONS: International centres observed large variations in care quality, with standards frequently sub-optimal. 71% of health care professionals would consider adopting the AS in their daily practice. Implementation in a low resource country resulted in significant improvements in some aspects of diabetes care. The AS checklist for diabetes care is a freely available in the public domain encompassing patient education, care plans, and educational resources for healthcare professionals including summary guidelines. The AS may provide a unique approach in delivering high quality diabetes care in countries with limited resources.

Challenges of emerging adulthood-transition from paediatric to adult diabetes.

Diabetes mellitus is a complex condition with far reaching physical, psychological and psychosocial effects. These outcomes can be significant when considering the care of a youth transferring from paediatric through to adult diabetes services. The art of mastering a smooth care transfer is crucial if not pivotal to optimising overall diabetic control. Quite often the nature of consultation varies between the two service providers and the objectives and outcomes will mirror this. The purpose of this review is to analyse the particular challenges and barriers one might expect to encounter when transferring these services over to an adult care provider. Particular emphasis is paid towards the psychological aspects of this delicate period, which needs to be recognised and appreciated appropriately in order to understand the particular plights a young diabetic child will be challenged with. We explore the approaches that can be positively adopted in order to improve the experience for child, parents and also the multi- disciplinary team concerned with the overall delivery of this care. Finally we will close with reflection on the potential areas for future development that will ultimately aim to improve long-term outcomes and experiences of the young adolescent confronted with diabetes as well as the burden of disease and burden of cost of disease.

The impact of improved glycaemic control with GLP-1 receptor agonist therapy on diabetic retinopathy.

Rapid improvement in glycaemic control with GLP-1 receptor agonist (RA) therapy has been reported to be associated with significant progression of diabetic retinopathy. This deterioration is transient, and continuing GLP-1 RA treatment is associated with reversal of this phenomenon. Pre-existent maculopathy, higher grade of retinopathy and longer duration of diabetes may be risk factors for persistent deterioration.

Cushing's disease: establishing the diagnosis and management approach.

A 64 year old lady, with a background history of type 2 diabetes mellitus and hypertension, presented with general deterioration of general health, poor glycemic control, difficulty in controlling blood pressure and difficulty in walking. She had past medical history of adenocarcinoma of the oesophagus, treated with surgery and subsequent chemotherapy. General examination revealed high blood glucose and blood pressure and a Cushingoid facies. Overnight dexamethasone suppression test and urinary free cortisol levels confirmed Cushing's syndrome and High dose dexamethasone suppression test showed partial suppression. CT scan of the abdomen showed bilateral hyperplasia of the adrenals with nodularity on the left side, raising the possibility of an adrenal adenoma. ACTH levels were elevated thereby ruling out autonomously functioning adrenal nodule, however increasing the possibility of ectopic ACTH secretion due to the previous medical history. MRI of the pituitary confirmed the presence of an adenoma, thereby pointing to the diagnosis of pituitary dependant Cushing's disease. The patient could not undergo further invasive investigation or surgery due to septicaemia. Medical management of Cushing's syndrome was resorted to in the interim with Ketoconazole, showing excellent response. This case depicts the need for a high index of suspicion for the diagnosis, the importance of organizing specific investigations in the appropriate order to arrive at a diagnosis and an effective management plan.

GLP-1 agonist treatment: implications for diabetic retinopathy screening.

Rapid improvement in glycaemic control induced by GLP-1 agonist therapy could be yet another illustration of transient or permanent progression of diabetic retinopathy, similar to documented examples such as pregnancy and continuous subcutaneous insulin infusion. Specific guidelines would be needed to monitor this paradoxical phenomenon during treatment with GLP-1 agonists.

Higher prevalence of retinopathy in diabetic patients of South Asian ethnicity compared with white Europeans in the community: a cross-sectional study.

OBJECTIVE: The purpose of this study was to compare prevalence and risk factors for diabetic retinopathy among U.K. residents of South Asian or white European ethnicity. RESEARCH DESIGN AND METHODS: This was a community-based cross-sectional study involving 10 general practices; 1,035 patients with type 2 diabetes were studied: 421 of South Asian and 614 of white European ethnicity. Diabetic retinopathy, sight-threatening retinopathy, maculopathy, and previous laser photocoagulation therapy were assessed after grading of retinal photographs. Data were collected on risk factors including age, duration, and treatment of diabetes, blood pressures, serum total cholesterol, and A1C. RESULTS: Patients of South Asian ethnicity had significantly higher systolic (144 vs. 137 mmHg, P < 0.0001) and diastolic (84 vs. 74 mmHg, P < 0.0001) blood pressure, A1C (7.9 vs. 7.5%, P < 0.0001), and total cholesterol (4.5 vs. 4.2 mmol/l, P < 0.0001). Diabetic retinopathy was detected in 414 (40%) patients (189 South Asian [45%] versus 225 white European [37%]; P = 0.0078). Sight-threatening retinopathy was detected in 142 (14%) patients (68 South Asian [16%] versus 74 white European [12%]; P = 0.0597). After adjustment for confounders, there were significantly elevated risks of any retinopathy and maculopathy for South Asian versus white European patients. CONCLUSIONS: Patients of South Asian ethnicity had a significantly higher prevalence of diabetic retinopathy and maculopathy, with significantly elevated systolic and diastolic blood pressure, A1C, and total cholesterol; lower attained age; and younger age at diagnosis. Earlier onset of disease and higher levels of modifiable risk factors make early detection of diabetes, annual referral for retinal screening, and intensive risk factor control key elements in addressing this health inequality.