Search

Abstract Background Familial partial lipodystrophy (FPLD) is an inherited disorder of white adipose tissue that causes premature cardiometabolic disease. There is no clear diagnostic criteria for FPLD, and this may explain the under-detection of this condition. Aim This pilot study aimed to describe the clinical features of women with FPLD and to explore the value of adipose tissue measurements that could be useful in diagnosis. Methods In 8 women with FPLD and 4 controls, skinfold measurements, DXA and whole-body MRI were undertaken. Results Whole genome sequencing was negative for monogenic metabolic causes, but polygenic scores for partial lipodystrophy were elevated in keeping with FPLD type 1. The mean age of diagnosis of DM was 31 years in the FPLD group. Compared with controls, the FPLD group had increased HOMA-IR (10.3 vs 2.9, p = 0.028) and lower mean thigh skinfold thickness (19.5 mm vs 48.2 mm, p = 0.008). The FPLD group had lower percentage of leg fat and an increased ratio of trunk to leg fat percentage on DXA. By MRI, the FPLD group had decreased subcutaneous adipose tissue (SAT) volume in the femoral and calf regions (p

Abstract Aims/Introduction Depression is prevalent in diabetes patients and associated with poor outcomes, but is currently underdiagnosed, with no firm consensus on screening methods. We evaluated the validity of the short‐form five‐item Problem Areas in Diabetes (PAID‐5) questionnaire as a screening tool for depression, comparing it with the Beck Depression Inventory‐II (BDI‐II) and nine‐item Patient Health Questionnaire (PHQ‐9). Materials and Methods A total of 208 English‐speaking adults with type 2 diabetes, recruited from outpatient clinics, completed the BDI‐II, PHQ‐9 and PAID‐5 questionnaires in English. Cronbach's α was used for internal reliability. Convergent validity was examined with BDI‐II and PHQ‐9. Receiver operating characteristics analyses were used to identify optimal PAID‐5 cut‐offs for the diagnosis of depression. Results All three screening tools were highly reliable, with BDI‐II, PHQ‐9 and PAID‐5 having a Cronbach's α of 0.910, 0.870 and 0.940, respectively. There was a good correlation between BDI‐II and PHQ‐9, with a correlation co‐efficient (r) of 0.73; and a moderate correlation between PAID‐5 and PHQ‐9, and PAID‐5 and BDI‐II, with r of 0.55 and 0.55 respectively (P values 14 (sensitivity 72%, specificity 784%, area under the curve 0.809) and a PHQ‐9 cut‐off >10 (sensitivity 84%, specificity 74%, area under the curve 0.806). Using a PAID‐5 cut‐off ≥9, the prevalence of depressive symptoms was 36.1%. Conclusions Depressive symptoms are prevalent in people with type 2 diabetes, with the degree of distress significantly related to the severity of depressive symptoms. PAID‐5 is a valid and reliable screening tool, and a score ≥9 could prompt further confirmation for depression.

ObjectivesThis study aims to investigate the prevalence of undiagnosed cardiovascular risk factors in patients with ischaemic heart disease (IHD).MethodsWe assessed the prevalence of previously undiagnosed cardiovascular risk factors, including elevated lipoprotein(a) [Lp(a)], among consenting patients with IHD who were admitted to hospital. Clinical information, including dietary history, from patients with newly diagnosed IHD and known IHD were compared.ResultsOf the 555 patients, 82.3% were males and 48.5% of Chinese ethnicity. Overall, 13.3% were newly diagnosed with hypertension, 14.8% with hypercholesterolemia, and 5% with type 2 diabetes (T2DM). Patients with newly diagnosed IHD, compared to those with known IHD, had a higher prevalence of new diagnoses of hypercholesterolemia (29.1% vs. 2.0%, p 50% of patients in both groups did not meet national recommendations for fruits, vegetables, wholegrain and oily fish intake. However, patients with known IHD had a more regular omega-3 supplement intake (23.4% vs. 10.3%, p = 0.024).ConclusionIncreased detection efforts is necessary to diagnose chronic metabolic diseases (hypertension, hypercholesterolemia, T2DM) especially among patients at high risk for IHD. Cardiovascular risk factors, in particular elevated Lp(a), smoking, and suboptimal dietary intake in patients with IHD deserve further attention.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors.Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia.Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (

Activating mutation of glucokinase gene (GCK) causes resetting of insulin inhibition at a lower glucose threshold causing hyperinsulinaemic hypoglycaemia (GCK-HH). This is the first reported case who tolerated years of regular fasting during Ramadhan, presenting only with seizure and syncope now. We describe a case with GCK gene variant p.T65I diagnosed in a 51-year-old woman with hypoglycaemia unawareness even at glucose level of 1.6 mmol/L. Insulin and C-peptide levels during hypoglycaemia were suggestive of hyperinsulinism, but at a day after intravenous glucagon, hypoglycaemia occurred with low insulin and C-peptide levels, pointing against insulinoma as the underlying aetiology. Imaging studies of the pancreas and calcium arterial stimulation venous sampling were unremarkable. A review of old medical records revealed asymptomatic hypoglycaemia years ago. Genetic testing confirmed activating mutation of GCK. Hypoglycaemia was successfully controlled with a somatostatin analogue. This case highlights the importance of consideration of genetic causes of hypoglycaemia in adulthood, especially when imaging is uninformative.

IntroductionPrimary aldosteronism (PA) is associated with increased risk of cardiovascular events. However, treatment of PA has not been shown to improve left ventricular (LV) systolic function using the conventional assessment with LV ejection fraction (LVEF). We aim to use speckle-tracking echocardiography to assess for improvement in subclinical systolic function after treatment of PA.MethodsWe prospectively recruited 57 patients with PA, who underwent 24-h ambulatory blood pressure (BP) measurements and echocardiography, including global longitudinal strain (GLS) assessment of left ventricle, at baseline and 12 months post-treatment.ResultsAt baseline, GLS was low in 14 of 50 (28.0%) patients. On multivariable analysis, GLS was associated with diastolic BP (P = 0.038) and glomerular filtration rate (P = 0.026). GLS improved post-surgery by −2.3, 95% CI: −3.9 to −0.6, P = 0.010, and post-medications by −1.3, 95% CI: −2.6 to 0.03, P = 0.089, whereas there were no changes in LVEF in either group. Improvement in GLS was independently correlated with baseline GLS (P < 0.001) and increase in plasma renin activity (P = 0.007). Patients with post-treatment plasma renin activity ≥1 ng/ml/h had improvements in GLS (P = 0.0019), whereas patients with persistently suppressed renin had no improvement. Post-adrenalectomy, there were also improvements in LV mass index (P = 0.012), left atrial volume index (P = 0.002), and mitral E/e’ (P = 0.006), whereas it was not statistically significant in patients treated with medications.ConclusionTreatment of hyperaldosteronism is effective in improving subclinical LV systolic dysfunction. Elevation of renin levels after treatment, which reflects adequate reversal of sodium overload state, is associated with better systolic function after treatment.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT03174847.

The management of diabetes mellitus in an insulin-dependent patient is challenging in the setting of concomitant antibody-mediated-insulin hypersensitivity. We report a case of a 62-year-old woman with pre-existing type 2 diabetes mellitus of 10 years duration who developed type 3 hypersensitivity reaction to insulin analogue detemir, and subsequently, severe diabetic ketoacidosis (DKA). She was C-peptide negative and was diagnosed with insulin-dependent diabetes. Despite increasing dose adjustments, insulin-meal matching, and compliance with insulin, she experienced episodes of unexpected hyperglycaemia and hypoglycaemia. The development of rash after detemir initiation and rapid progression to DKA suggests an aberrant immune response leading to the insulin allergy and antibody-induced interference with insulin analogues. Glycaemic control in the patient initially improved after being started on subcutaneous insulin infusion pump with reduced insulin requirements. However, after a year on pump therapy, localised insulin hypersensitivity reactions started, and glycaemic control gradually deteriorated.

A previously well 32-year-old Chinese male presented with acute bilateral upper and lower limb paralysis upon waking, ten days after the onset of COVID-19 infection. Examination revealed areflexia over all four limbs, associated with reduced muscle strength, but no sensory or cranial nerve deficit. Initial concern was Guillain-Barre syndrome given the acute flaccid paralysis following COVID-19 infection. However, investigations revealed severe hypokalaemia (1.7 mmol/L) and primary hyperthyroidism. He was treated for thyrotoxic periodic paralysis (TPP) with β-blockers, antithyroid medications, and intravenous potassium chloride (KCl). Despite frequent monitoring of potassium, rebound hyperkalaemia occurred with prompt resolution of paralysis.

Cushing’s syndrome (CS) secondary to ectopic adrenocorticotrophic hormone (ACTH)-producing prostate cancer is rare with less than 50 cases reported. The diagnosis can be challenging due to atypical and variable clinical presentations of this uncommon source of ectopic ACTH secretion. We report a case of Cushing’s syndrome secondary to prostate adenocarcinoma who presented with symptoms of severe hypercortisolism with recurrent hypokalaemia, limb oedema, limb weakness, and sepsis. He presented with severe hypokalaemia and metabolic alkalosis (potassium 2.5 mmol/L and bicarbonate 36 mmol/L), with elevated 8 am cortisol 1229 nmol/L. ACTH-dependent Cushing’s syndrome was diagnosed with inappropriately normal ACTH 57.4 ng/L, significantly elevated 24-hour urine free cortisol and unsuppressed cortisol after 1 mg low-dose, 2-day low-dose, and 8 mg high-dose dexamethasone suppression tests. 68Ga-DOTANOC PET/CT showed an increase in DOTANOC avidity in the prostate gland, and his prostate biopsy specimen was stained positive for ACTH and markers for neuroendocrine differentiation. He was started on ketoconazole, which was switched to IV octreotide in view of liver dysfunction from hepatic metastases. He eventually succumbed to the disease after 3 months of his diagnosis. It is imperative to recognize prostate carcinoma as a source of ectopic ACTH secretion as it is associated with poor clinical outcomes, and the diagnosis can be missed due to atypical clinical presentations.

Abstract Background There is a global pandemic of type 2 diabetes mellitus (T2DM), especially in Asia. Singapore has a prevalence of T2DM at 10.5%, which is higher than the world average of 8.8%. Multiple studies have shown that multidisciplinary, team-based, coordinated care has been associated with improved measures of quality care and reduced healthcare utilization. Patients with poor glycemic control and nephropathy are at the highest risk of developing cardiovascular complications and renal failure. In this study, we aimed to investigate the impact of intensive multidisciplinary diabetes mellitus care with patient empowerment versus routine clinical care on the rate of progression of micro and macrovascular complications and peripheral atherosclerotic burden, as measured by changes in femoral intima-media thickness (IMT) in patients with persistently elevated HbA1c and nephropathy. Methods The study is a single-center randomized controlled trial (RCT) with two study arms - intensive diabetes mellitus care versus routine clinical care. Patients in the intensive arm will receive care from a multidisciplinary team consisting of an endocrinologist, diabetes nurse educator, dietitian, renal pharmacist and medical social worker for counselling. In addition, patients will be provided with tools for self-care empowerment such as glucometers, blood pressure monitors and android tablets to facilitate care, monitoring and education. Patients in the routine clinical care arm will receive standard clinical care. Follow up (FU) will be for 3 years. Primary outcomes include cardiovascular events, rate of progression of nephropathy and development of end-stage renal disease. Secondary endpoints include the proportions of patients with documented improved control of cardiovascular risk factors (HbA1c, blood pressure, low density lipoprotein-C (LDL-C), reduction in body weight), frequency of hypoglycemia, hospitalization days and changes in femoral IMT. We will also examine the prevalence of peripheral atherosclerosis and the predictive value and usability of lower extremity arterial ultrasound to predict cardio-cerebrovascular events, amputation and peripheral intervention. Discussion Diabetes mellitus carries significant healthcare costs. Patients with poor glycemic control and nephropathy are at highest risk of developing cardiovascular complications and renal failure. Intensive diabetes mellitus care with patient empowerment may lead to sustained glycemic control, reduction of clinical complications and progression of nephropathy, and incidence of cardiovascular complications. Trial registration ClinicalTrials.gov, NCT03413215. Registered on 29 January 2019.

BackgroundDiabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans.MethodsWe compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco's Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water.ResultsELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo.ConclusionsELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.

Objective: Migrant workers, a marginalized and under-resourced population, are vulnerable to coronavirus disease 2019 (COVID-19) due to limited healthcare access. Moreover, metabolic diseases—such as diabetes mellitus (DM), hypertension, and hyperlipidemia—predispose to severe complications and mortality from COVID-19. We investigate the prevalence and consequences of undiagnosed metabolic illnesses, particularly DM and pre-diabetes, in international migrant workers with COVID-19.Methods: In this retrospective analysis, we analyzed the medical records of international migrant workers with laboratory-confirmed COVID-19 hospitalized at a tertiary hospital in Singapore from April 21 to June 1, 2020. We determined the prevalence of DM and pre-diabetes, and analyzed the risk of developing complications, such as pneumonia and electrolyte abnormalities, based on age and diagnosis of DM, and pre-diabetes.Results: Two hundred and fouty male migrant workers, with mean age of 44.2 years [standard deviation (SD), 8.5years], were included. Twenty one patients (8.8%) were diagnosed with pre-diabetes, and 19 (7.9%) with DM. DM was poorly controlled with a mean HbA1c of 9.9% (SD, 2.4%). 73.7% of the patients with DM and all the patients with pre-diabetes were previously undiagnosed. Pre-diabetes was associated with higher risk of pneumonia [odds ratio (OR), 10.8, 95% confidence interval (CI), 3.65–32.1; P < 0.0001], hyponatremia (OR, 8.83; 95% CI, 1.17–66.6; P = 0.0342), and hypokalemia (OR, 4.58; 95% CI, 1.52–13.82; P = 0.0069). Moreover, patients with DM or pre-diabetes developed COVID-19 infection with lower viral RNA levels.Conclusions: The high prevalence of undiagnosed pre-diabetes among international migrant workers increases their risk of pneumonia and electrolyte abnormalities from COVID-19.

Introduction: Whether parathyroidectomy is more beneficial to renal function when compared to medical therapy or observation in primary hyperparathyroidism (PHPT) is unclear. Neither has this premise been explored in non-Caucasian populations. The estimated glomerular filtration rate (eGFR) threshold below which parathyroid hormone (PTH) levels rise if at all in PHPT has also not been established. We determined if surgery was superior to medical therapy and observation in a multi-ethnic Asian patient population with PHPT and whether there was an eGFR threshold below which PTH levels further increased in them. Methods: Retrospective evaluation of patients with PHPT. Results: There were 68.6% Chinese, 17.4% Malays, 10.7% Indians, and 3.3% Eurasians. The median (interquartile range) follow-up was 18.0 months (4.5–46.8). At last follow-up, eGFR in the surgical (80 ± 30 ml/min) was higher than the medical (52 ± 32 ml/min) or observation groups (48 ± 33 ml/min); P < 0.01. This difference persisted after adjusting for age, gender, ethnicity, pre-intervention eGFR levels, nephrolithiasis, serum calcium, phosphate, urinary calcium, and duration of follow-up; P = 0.035. There was no definite eGFR level below which PTH values rose. Conclusion: Our study provides compelling evidence that in PHPT, surgery may be associated with a better renal outcome compared to medical management or observation. This has to be confirmed through prospective randomized controlled trials and the reasons for this finding have to be elucidated through functional and histological measures. The finding in our study of a lack of a specific eGFR threshold below which PTH levels further rose challenges the concept of a fixed renal threshold for secondary elevations of PTH in PHPT.

Joan Khoo, Christopher K Rayner, Karen L Jones, Michael HorowitzDiscipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, AustraliaAbstract: The advent of ‘incretin-based therapies’ – GLP-1 agonists and dipeptidyl-peptidase-4 inhibitors – which result in improvements in glycemic control comparable to those with existing oral hypoglycemic agents, and potentially improve cardiovascular and pancreatic β-cell function, represents a major therapeutic advance in the management of type 2 diabetes. Gastrointestinal adverse effects occur commonly with GLP-1 agonists, and rarely with DPP-4 inhibitors, but are dose-dependent and usually transient. The low risk of hypoglycemia, and beneficial or neutral effects on body weight, render GLP-1 agonists and DPP-4 inhibitors suitable alternatives to insulin secretagogues and insulin in overweight and elderly patients. Incretin-based therapies also improve quality of life in patients with type 2 diabetes, and may be cost-effective in the long term.Keywords: incretin, type 2 diabetes, therapy, GLP-1, DPP-4

Obesity, defined as a condition of excessive body fat with adverse effects on health, is an increasing global problem which contributes to chronic disease burden and health care costs. The Singapore Ministry of Health (MOH) released Clinical Practice Guidelines (CPG) in 2004, aimed at providing best evidence-based recommendations for diagnosis, classification, evaluation and multidisciplinary management (diet, physical activity, medication and surgery) of overweight and obesity in adults and the pediatric population. This article summarizes the guidelines, discusses their utility in Singapore and strategies for increasing their use, and briefly outlines updates in management since the CPG’s publication. A revised CPG is urgently needed in view of the increasing prevalence of overweight and obesity in Singapore and the numerous advances in the management of overweight and obesity.

A 54-year- old woman with insulin-requiring type 2 diabetes mellitus presented with acute shortness of breath and drowsiness on a background of polydipsia, weakness and significant weight loss. One year ago, she had decided to stop her insulin and other medications and adopt lifestyle modifications instead. Initial emergency department (ED) blood samples were highly lipaemic and appeared strawberry pink. She was eventually diagnosed with diabetic ketoacidosis (DKA) with severe hypertriglyceridaemia, intubated for airway protection, and managed with fluid resuscitation and intravenous insulin to good effect. We share an uncommon DKA presentation at the ED. History was limited as the patient was drowsy and minimally communicative. Physical examination was unremarkable. Blood investigations were also delayed in view of the need for additional centrifugation. These contributed to a paucity of information in the acute setting and resulted in a diagnostic challenge. [ABSTRACT FROM AUTHOR]

Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. [ABSTRACT FROM AUTHOR]