Achieving and maintaining good glycaemic control remains an important goal in the management of this common and prevalent disorder. Recent evidence from important megatrials, ACCORD, ADVANCE, VADT, UKPDS-10 year follow-up as well as the STENO-2 follow-up study, have cleared doubts concerning the benefits of targeting good glycaemic control. For the first time, we have the reassurance that macrovascular benefits can be realised from good glycaemic control. The legacy effect of prior good glucose control from the UKPDS-10 year follow-up, reinforces the results seen from the DCCT-EDIC (for Type 1 diabetes). The Intervention Phase of the UKPDS revealed benefits for reduction of microvascular complications, while it was only at the end of the Post-Trial Monitoring Phase where significant improvements in both micro and macrovascular outcomes were seen. The other three Trials assessing the effect of glycaemic control on cardiovascular outcomes, although largely negative for CV benefit, give valuable insight towards appropriate patient characteristics for which aggressive glucose control can and should be instituted. Individualising glycaemic targets, which has been the approach that many clinicians have been practising, has received new impetus albeit with clearer details. Getting to glycaemic goal early in the course of T2DM and Doing to Safely (Avoiding hypoglycaemia) are the key ingredients to successful management. The legacy of the memory of initial good metabolic/glycaemic control is investment in good health with benefits of reductions in both micro and more importantly, macrovascular disease, years later. Multifactorial interventions that include blood pressure, lipid lowering in addition to glucose control in these individuals with the Metabolic Syndrome result in more immediate beneficial additive effects on cardiovascular outcomes.
Diabetes Complications

Osteoporosis ; Postmenopause ; Malaysia ; Calcium ; Therapeutics

Tumour-induced or oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome characterized by bone pain and muscle weakness. A biochemical profile consisting of normocalcaemia, hypophosphataemia, phosphaturia, increased serum alkaline phosphatase and inappropriately low serum levels of 1, 25-dihydroxyvitamin-D is diagnostic. OOM is usually caused by an osseous or soft-tissue tumour of mesenchymal origin that secretes phosphaturic substances leading to increased urinary phosphate wasting. These tumours are small and slow growing. The diagnosis continues to be easily missed and when eventually made, localization of the tumour can be difficult. We describe the case of a young man who presented with severe generalized pain associated with muscle weakness. He was extensively investigated and eventually diagnosed to have OOM 3 years after initial presentation. Specialized investigations were necessary to localize the offending tumour.

Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well, but some may develop rare life threatening side effects such as agranulocytosis and aplastic anaemia. Clinical experience with the latter condition is extremely limited. We report on a case of carbimazole-induced aplastic anaemia caused by hypocellular bone marrow and associated plasmacytosis in a thyrotoxic patient chronically treated with carbimazole. This resolved after substitution with propylthiouracil. The clinical course was complicated by neutropaenic septicaemia and atrial fibrillation.
Thyrotoxicosis

Background: Psoriasis has been shown to be associated with a higher risk of metabolic syndrome and cardiovascular disease. Objective: To investigate the prevalence of metabolic syndrome among patients with psoriasis and study the association between psoriasis and cardiovascular risk factors. Methods: This was a hospital based case-control study conducted at the Dermatology Clinic, University Malaya Medical Centre (UMMC) from May 2010 to March 2011. A total of 131 adult patients with psoriasis and 129 age-, gender- and race-matched controls were recruited. All subjects answered a standardised cardiovascular risks questionnaire and had anthropometric measurements recorded. Laboratory investigations included fasting glucose / lipid profile, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), urine microalbumin:creatinine ratio and an electrocardiogram. The diagnosis of metabolic syndrome was made using the harmonised criteria for metabolic syndrome in South East Asians. Statistical analysis was performed using statistical processing software (SPSS-17). Results: Metabolic syndrome was significantly higher among patients with psoriasis (64.9% versus 51.9%) (p = 0.034). The presence of metabolic syndrome was associated with low high density lipoprotein (HDL) (p=0.002) and high triglyceride (TG) levels (p = 0.014). The prevalence of diabetes mellitus was also significantly higher among patients with psoriasis (46.6% versus 27.1%) (p = 0.001). Hypertension, ischaemic heart disease, low density lipoprotein (LDL) levels, smoking and obesity were not significantly higher among patients with psoriasis. Conclusion: Our results demonstrate an association between psoriasis and metabolic syndrome which was primarily due to diabetes mellitus and dyslipidaemia.

We report a 33-year-old Malay lady who presented with fever, tonsillitis and pharyngitis a month after initiation of antithyroid therapy (carbimazole 15 mg tds) for thyrotoxicosis by her general practitioner. She was still clinically and biochemically thyrotoxic but not in thyroid storm. At that time, she was also confirmed to be four weeks pregnant. Her full blood count revealed neutropaenia with an absolute neutrophil count of 0.036 × 109/L. Bone marrow aspirate and trephine were compatible with carbimazole-related agranulocytosis. Carbimazole was discontinued and she was given broad spectrum antibiotics and Granulocyte Colony Stimulating Factor (GCSF), to which she responded. Verapamil was used for symptomatic heart rate control instead of beta-blockers as she had a history of bronchial asthma. The patient subsequently opted for termination of pregnancy after which she was given radioactive iodine I131 (10 mCi) for definitive therapy of her thyrotoxicosis. In conclusion, carbimazole-related agranulocytosis is an important entity to recognise and treat early to prevent morbidity and mortality. Termination of pregnancy was carried out as the treatment given during the episode of agranulocytosis may have negative effects on foetal viability and growth.

Objective: To evaluate the cost-effectiveness of olaparib as a maintenance treatment versus routine surveillance (RS) in patients with BRCA mutated (BRCAm) advanced ovarian cancer (OC) following response to first-line platinum-based chemotherapy in Singapore. Methods: A 4-health state partitioned survival model was developed to simulate the lifetime (50 years) incremental cost-effectiveness ratio (ICER) of olaparib versus RS from a healthcare payer perspective. Progression-free survival, time to second disease progression, and overall survival were estimated using SOLO-1 data and extrapolated beyond the trial period using parametric survival models. Any patient who remained progression-free at year 7 was assumed to be no longer at risk of progression. Mortality rates were based on all-cause mortality, adjusted based on BRCA1/2 mutation. Health state utilities and adverse event frequencies were from SOLO-1. Drug costs were from local public healthcare institutions. Healthcare resource usage and costs were from local clinician input and publications. A 3% discount rate was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of results. Results: The base-case analysis of olaparib maintenance therapy versus RS resulted in an ICER of Singapore dollar (SGD) 19,822 per quality-adjusted life-year (QALY) gained. The ICER was most sensitive to variations in the discount rate. PSA demonstrated that olaparib had an 87% probability of being cost-effective versus RS at a willingness-to-pay of SGD 60,000 per QALY gained. Conclusion Olaparib has a high potential of being a cost-effective maintenance treatment versus RS for patients with BRCA1/2m advanced OC after response to first-line chemotherapy in Singapore.