Glycated haemoglobin trajectories and one-year risk of potentially avoidable hospitalisations among adult patients with type 2 diabetes from specialist outpatient clinics of a tertiary hospital: A cohort study.

AIM: To evaluate the association between trajectories of glycated haemoglobin (HbA1c) and potentially avoidable hospitalisations (PAH). METHODS: We performed a cohort study in a tertiary hospital in Singapore among adult type 2 diabetes patients with ≥ 3 HbA1c tests over two years. Then, we followed up for one year after the last HbA1c reading to determine the PAH outcome. Glycaemic control was analysed by (1) HbA1c trajectories through group-based trajectory modelling, and (2) mean HbA1c. PAH was defined using the Agency of Healthcare Research and Quality criteria, categorising as overall, diabetes, acute, and chronic-composites. RESULTS: A total of 14,923 patients (mean age: 62.9 ± 12.8 years; 55.2% men) were included. Four HbA1c trajectories were observed; low-stable (n = 9854, 66.0%), moderate-stable (n = 3125, 20.9%), high-decrease (n = 1017, 6.8%) and high-persistent (n = 927, 6.2%). Compared to the low-stable trajectory, one-year risk ratio (RR) and 95% confidence interval (CI), respectively for moderate-stable, high-decrease and high-persistent trajectories were as follows: (1) overall PAH: 1.15 (1.00-1.31), 1.53 (1.31-1.80), 1.96 (1.58-2.43); (2) diabetes PAH: 1.30 (1.04-1.64), 1.98 (1.55-2.53), 2.24 (1.59-3.15); (3) acute PAH: 1.14 (0.90-1.44), 1.29 (0.95-1.77), 1.75 (1.17-2.62); and (4) chronic PAH: 1.21 (1.02-1.43), 1.62 (1.34-1.97), 2.14 (1.67-2.75). Mean HbA1c was significantly associated with overall and chronic-composites of PAH whilst evidence of a non-linear relationship with diabetes-composite of PAH was noted. CONCLUSION: Patients with high-decrease trajectory had a risk lower than those with persistently-high HbA1c, highlighting that a greater risk of hospitalisation conferred by poor glycaemic control is potentially reversible. Determining HbA1c trajectories could help to identify the high-risk individuals for targeted and intensive management to improve care and reduce hospitalisations.

SARS-CoV-2 mRNA Vaccination and Graves' Disease: A Report of 12 Cases and Review of the Literature.

CONTEXT AND OBJECTIVE: Thyroid autoimmunity has been reported to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the SARS-CoV-2 vaccination recently. We report a series of patients who presented with new onset or relapse of Graves' disease-related hyperthyroidism shortly after receiving the SARS-CoV-2 messenger RNA (mRNA) vaccine at a single tertiary institution in Singapore. METHODS AND RESULTS: We describe 12 patients who developed hyperthyroidism within a relatively short interval (median onset, 17 [range, 5-63] days) after receiving the SARS-CoV-2 mRNA vaccine. The majority were females (11/12) with median age of 35.5 (range, 22-74) years. Six patients had new-onset hyperthyroidism, whereas the other 6 had relapse of previously well-controlled Graves' disease. TSH receptor antibody concentrations ranged from 2.4 to 32 IU/L. The majority of the patients were able to go for the second dose of the vaccine without any further exacerbations. Literature review revealed 21 other similar cases reported from across the world. CONCLUSION: Our case series provides insight into the characteristics of individuals in whom Graves' disease was triggered by the SARS-CoV-2 vaccination. Clinicians need to be vigilant of precipitation or exacerbation of autoimmune thyroid disorders in predisposed individuals after exposure to the SARS-CoV-2 vaccination. Further epidemiological and mechanistic studies are required to elucidate the possible associations between the SARS-CoV-2 vaccines and the development of thyroid autoimmunity.

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism.

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Adefovir-induced Fanconi syndrome: diagnostic pearls and perils of late or missed diagnosis.

Low-dose adefovir therapy has been increasingly recognised as a cause of Fanconi syndrome. Being relatively novel, early diagnosis is both fraught with difficulty and yet of paramount importance given its far-reaching consequences, many of which are amenable to treatment. We discuss a patient who presented with hypokalemia and other electrolyte abnormalities suggestive of Fanconi syndrome whilst on adefovir for hepatitis B. A trans-tubular potassium gradient (TTKG = 9.4) and urinary fractional phosphate excretion (39.4 %) consistent with renal potassium and phosphate wasting together with euglycemic glycosuria, aminoaciduria and hypophosphatemic osteomalacia supported the diagnosis of adefovir-induced Fanconi syndrome. With the cessation of the culprit drug, the patient has achieved partial recovery after 9 months. A high index of suspicion coupled with regular symptom surveillance and electrolyte monitoring is recommended in the course of adefovir therapy.