M Al‐Mrayat

Peer advisers compared with specialist health professionals in delivering a training programme on self-management to people with diabetes: a randomized controlled trial

Aims  To assess the effectiveness and acceptability of peer advisers in diabetes in delivering a programme of training on self‐management for people with diabetes.

Tolerability of prolonged-release metformin (Glucophage® SR) in individuals intolerant to standard metformin — results from four UK centres

Advances in drug formulation have improved the tolerability of many commonly used agents. Metformin is recommended as initial drug therapy for type 2 diabetes and has proven long-term efficacy and safety. However, gastrointestinal (GI) side-effects of standard, immediate-release (IR) metformin often reduce medication adherence and limit dose titration. A prolonged-release metformin formulation may improve tolerability over its IR counterpart. We report the results of two prospective and two retrospective clinic-based evaluations of the tolerability of metformin in a total of 95 patients intolerant to standard IR metformin assessed over three to six months following a switch from IR to prolonged-release metformin (Glucophage® SR). Between 62% and 100% of patients from the centres tolerated the prolonged-release formulation. Glycaemia following the switch was improved or unchanged. Prolonged-release metformin represents a useful option for patients intolerant of standard IR metformin due to GI side-effects. This improved tolerance of prolonged-release metformin may improve medication adherence and thereby enhance treatment outcomes. Br J Diabetes Vasc Dis 2007;7:225-8

SDHA mutated paragangliomas may be at high risk of metastasis

We report the clinical outcomes of eleven patients with succinate dehydrogenase subunit A (SDHA) germline mutations from three UK tertiary referral centres to highlight a more diverse and expanding clinical spectrum of associated phenotypes. We suggest that SDHA paraganglioma-related disease is not a low-risk condition as first described. Of our six index cases, two developed metastatic disease and a further one had local vascular invasion. One patient developed multiple metachronous disease. Therefore, we believe these patients, like those with SDHB and SDHD mutations, should be part of a surveillance programme. Paraganglioma (PGL)-associated mutations in SDHA have only been reported in a small number of patients worldwide. There is controversy over the necessity for surveillance screening in these patients, compared to SDHB and SDHD, as penetrance is thought to be lower (Benn et al. 2015) and variants exist with uncertain pathogenicity. Initial reports associated SDHA with autosomal recessive causes of juvenile encephalopathy (Leigh syndrome) (Bourgeron et al. 1995) and homozygous mutations in SDHA cause severe neurological dysfunction and cardiomyopathy (Renkema et al. 2015). SDHA mutations have now been associated with phaeochromocytoma and paraganglioma (PPGL) formation in an autosomal dominant manner. SDHA mutations account for only 3% of cases of familial PGL cases, with presumed low penetrance (Korpershoek et al. 2011) and therefore very little data on clinical features of SDHA-related PPGL exist. Six index cases were originally diagnosed between 1973 and 2011 and had histologically proven PPGL, who subsequently underwent genetic testing during the course of their follow-up and were confirmed to have an underlying SDHA germline mutation. We performed a retrospective analysis of their notes and describe their clinical outcomes. From these six index cases, cascade genetic testing occurred and identified five further asymptomatic carriers of SDHA mutations. All patients are now being followed up in specialised endocrine clinics and are undergoing annual screening, including annual clinical and biochemical assessment and cross-sectional imaging, although the frequency and modality of imaging differs between centres. To predict the pathogenicity of the DNA variants, the missense variants were investigated in silico using PloyPhen2 and SIFT. Table 1 provides a detailed summary of the patients described. The six index patients originally presented were aged 18, 34, 36, 46, 47 and 68 years. Five patients presented with a single lesion at diagnosis: intrathyroidal PGL, mediastinal PGL, phaeochromocytoma and two extraadrenal PGLs. One patient (patient 3) presented with two synchronous lesions: she had a 3-methoxytyramine (3MT)-secreting carotid body tumour and a noradrenalinesecreting thoracic PGL. All patients underwent surgical resection of the primary tumours. Two patients developed recurrence in the surgical bed and both patients went on to develop metastatic disease 16 and 37 years later (patients 8 and 9). One of these two patients (patient 8) also developed an additional five metachronous lesions 7–10 years after original diagnosis. These two cases are described in more detail. Patient 8 presented aged 46 years with headaches and malignant hypertension (210/130 mmHg). Urinary noradrenaline was very raised (Table 1) and imaging confirmed a 5 cm para-adrenal PGL, which was subsequently resected. He developed a symptomatic recurrence one year later, which was surgically resected. Eight years after his original diagnosis, he presented with symptoms of catecholamine excess and four new lesions were identified and resected. On surveillance imaging three years later, a new non-secretory lesion was identified. Surgical resection was undertaken one year subsequently due to increasing PGL size and plasma catecholamine levels. He remained well with no evidence of further disease on imaging until five years later when rising noradrenaline levels were noted and uptake in the left adrenal bed and in the vertebral body of L4 was

Dapagliflozin: NICE guidance for use in combination therapy for the treatment of type 2 diabetes

AstraZeneca)1 is a competitive, reversible, and highly selective inhibitor of a major renal sodium glucose co-transporter (SGLT2) resulting in insulinindependent renal elimination of glucose (a glucuretic effect).2 Paradoxically, the ensuing glucosuria, once an undesirable facet of diabetes, is now an innovative therapeutic mechanism utilised by dapagliflozin which is licensed for use as monoand add-on therapy, including with insulin in adults with type 2 diabetes, but not with pioglitazone.3 Dapagliflozin appears on average to reduce HbA1c by 0.54% and weight by 1.8kg.4 Given SGLT2 inhibitors’ mechanism of action, there is a reported increased risk of urinary and genital tract infections (OR of 1.34).5 The recently renamed National Institute for Health and Care Excellence (NICE) issued its single technology appraisal (STA) on the clinical use of dapagliflozin in June 2013.6 Following its deliberation and evidence consideration, NICE has supported the selective use of dapagliflozin in adults with type 2 diabetes in dual therapy and with insulin. The summary of the recommendations is outlined in Table 1.

Prolonged release exenatide gets the go-ahead from NICE

he use of glucagon-like peptide-1 (GLP-1) based therapies in the treatment of type 2 diabetes has become well established in clinical practice within the UK since the launch of the first GLP-1 analogue, exenatide, in 2007 and subsequently that of liraglutide in 2009. Trends towards increased use of GLP-1 can be inferred from national prescribing data showing that the cost per item in the ‘other anti-diabetic drugs’ category, primarily consisting of GLP-1 analogues, has increased substantially by 144% since 2007, while that for other diabetes drug categories has remained fairly stable. 1 The reason for the increasing use of GLP-1 analogues probably derives from proven efficacy in lowering blood glucose levels combined with beneficial effects on weight and potentially blood pressure which is in contrast to many other therapeutic modalities in diabetes. 2 Exenatide prolonged release (EPR) is the first onceweekly GLP-1 analogue to come to the market with a UK licence (as Bydureon) for use in combination with oral antidiabetic therapy in the treatment of type 2 diabetes. The National Institute for Health and Clinical Excellence (NICE) issued its single technology appraisal (STA) on the use of this agent in February 2012. 3 Based upon its analysis of the available clinical data and application of cost-effectiveness modelling, the NICE Evidence Review Group has concluded in support of the use of EPR as a cost-effective alternative to the previously established daily GLP-1 analogues, with the main additional clinical benefit being of fewer injections which could potentially reduce the impact of managing type 2 diabetes on the daily lives of patients and their carers. The recommendations for initiation and discontinuation of EPR are summarised in Table 1 and are essentially the same as those for the two established GLP-1 analogues, twice-daily exenatide and once-daily liraglutide (NICE CG87 & TA203, respectively). 4,5 Review of the evidence informing the guidance

A new cause of neuroglycopenia: "missing the point".

Confirmation of diagnosis of hypoglycaemia with capillary blood glucose measurement is often undertaken by patients when they develop symptoms of a low glucose level. This then leads to appropriate dietary action and resolution of hypoglycaemia. We report a case of severe hypoglycaemia in a previously fit 90-year-old retired army surgeon with Type 2 diabetes who had misread the glucometer sensor display. He was falsely reassured, despite symptoms, by reading ‘17’ mmol/ l when the actual result was 1.7 mmol/ l, and so did not take any immediate action. His medication comprised gliclazide 40 mg od, metformin 850 mg bd, and omperazole 20 mg od. He was subsequently admitted to the emergency department following collapse. On admission he had right-sided hemiparesis and speech difficulty in association with a plasma glucose of 1.4 mmol/ l. Intravenous dextrose (50%) was administered with immediate and complete resolution of his weakness and speech impairment. During the next 24 h and following withdrawal of hypoglycaemic agents, his glucose remained above 5.0 mmol/ l. The importance of the visual clarity of display on glucometer sensors has never been formally assessed to our knowledge. At present, the majority of glucometer sensors display the decimal point at the bottom of the screen, in a variety of sizes, which can easily be ignored, particularly during visual disturbance associated with hypoglycaemia. Improving the position and size of the decimal point display, as well as increasing the awareness of this pitfall in design for patients and their professional educators, will avoid potential cases of neuroglycopenia due to ‘missing the point’.