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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

IntroductionTriglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels.AimThis study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals.MethodsA 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory.ResultsThe study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD (n = 14,704), 23.7% had an LDL-C level of 0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population.

Context: Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery. Objective: To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA. Design: Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019. Patients: 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy. Measurements: Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control. Results: Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32–2.67), p =.89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p =.02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0–2.0) versus 2.6 (IQR 0.8–4.3), p <.001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery. Conclusion: In patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA. [ABSTRACT FROM AUTHOR]

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 (

Chylomicronemia has either a monogenic or multifactorial origin. Multifactorial chylomicronemia is the more common form and is due to the interaction of genetic predisposition and secondary factors such as obesity, diabetes, unhealthy diet, and medications. We report a case of a 38-year-old man who was diagnosed with multifactorial chylomicronemia following presentation with a subarachnoid hemorrhage requiring emergency surgery through a burr hole; lactescent cerebrospinal fluid mixed with blood was observed through the burr hole. The serum triglyceride concentration was 52⋅4 mmol/L with a detectable triglyceride concentration in the cerebrospinal fluid. Rapid weight gain leading to obesity and related unfavorable lifestyle factors were identified as key secondary causes of chylomicronemia. Gene testing revealed a homozygous variant in APOA5 and a heterozygous common variant in GPIHBP1. Accompanied with secondary causes, the interactions of gene and environmental conditions contribute to chylomicronemia. With aggressive medical treatment including excess weight loss, healthy diet, cessation of alcohol, and combination of anti-lipemic medications, normal plasma triglyceride levels were achieved.

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.

Background: In addition to increased cardiovascular risk, patients with primary aldosteronism (PA) also suffer from impaired health-related qual ity of life (HRQoL) and psychological symptoms. We assessed for changes in HRQoL and de pressive symptoms in a cohort of Asian patients with PA, after surgical and medical therapy. Methods: Thirty-four patients with PA were prospectively recruited and completed questionnaires from 2017 to 2020. HRQoL was assessed using RAND -36 and EQ-5D-3L, and depressive symptoms were assessed using Beck Depression Inventory (BDI-II) at baseline, 6 months, and 1 year post-treatment. Results: At 1 year post-treatment, significant improvement was observed in both physical and mental summative scores of RAND-36, +3.65, P = 0.023, and +3.41, P = 0.033, respectively, as well as four subscale domains (physical functioning, bodily pain, role emotional, and mental health). Significant improvemen t was also seen in EQ-5D dimension of anxiety/depression at 1 year post-treatment. Patients treated with surgery (n = 21) had significant improvement in EQ-5D index score post-treat ment and better EQ-5D outcomes compared to the medical group (n = 13) at 1 year post-treatment. 37.9, 41.6 and 58.6% of patients had symptoms in the cognitive, affective and somatic domains of BDI-II, respectively. There was a significant improve ment in the affective domain of BDI-II at 1 year post-treatment. Conclusion: Both surgical and medical therapy improve HRQoL and psychologi cal symptoms in patients with PA, with surgery providing better outcomes. This highlights the importance of early diagnosis, accurate subtyping and appropriate treatment of PA.

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.

We present two cases of severe hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with very high urine sodium concentrations (>130 mmol/L). The first patient had hyponatremia from traumatic brain injury (TBI) while the second case had a history of recurrent SIADH triggered by various causes including gastritis. In both cases, fluid administration and/or consumption worsened the hyponatremia. Although a low urine sodium of 500 mOsm/kg), persistence of high urine sodium concentrations may be useful to predict poor response to fluid restriction in SIADH. More studies are needed to delineate treatment pathways of patients with very high urine osmolality and urine sodium concentrations in SIADH.

Elevated lipoprotein(a) [Lp(a)], a predominantly genetic disorder, is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valvular disease, particularly in patients with familial hypercholesterolemia (FH), a Tier I genomic condition. The combination from birth of the cumulative exposure to elevated plasma concentrations of both Lp(a) and low-density lipoprotein is particularly detrimental and explains the enhanced morbidity and mortality risk observed in patients with both conditions. An excellent opportunity to identify at-risk patients with hyper-Lp(a) at increased risk of ASCVD is to test for hyper-Lp(a) during cascade testing for FH. With probands having FH and hyper-Lp(a), the yield of detection of hyper-Lp(a) is 1 individual for every 2.1–2.4 relatives tested, whereas the yield of detection of both conditions is 1 individual for every 3–3.4 relatives tested. In this article, we discuss the incorporation of assessment of Lp(a) in the cascade testing in FH as a feasible and crucial part of models of care for FH. We also propose a simple management tool to help physicians identify and manage elevated Lp(a) in FH, with implications for the care of Lp(a) beyond FH, noting that the clinical use of RNA therapeutics for specifically targeting the overproduction of Lp(a) in at risk patients is still under investigation.

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.

Severe hyponatremia and osmotic demyelination syndrome (ODS) are opposite ends of a spectrum of emergency disorders related to sodium concentrations. Management of severe hyponatremia is challenging because of the difficulty in balancing the risk of overcorrection leading to ODS as well as under-correction causing cerebral oedema, particularly in a patient with chronic hypocortisolism and hypothyroidism. We report a case of a patient with Noonan syndrome and untreated anterior hypopituitarism who presented with symptomatic hyponatremia and developed transient ODS.

From our monogenic diabetes registry set-up at a secondary-care diabetes center, we identified a nontrivial subpopulation (~15%) of maturity-onset diabetes of the young (MODY) among people with young-onset diabetes. In this report, we describe the diagnostic caveats, clinical features and long-term renal-trajectory of people with HNF1B mutations (HNF1B-MODY). Between 2013 and 2020, we received 267 referrals to evaluate MODY from endocrinologists in both public and private practice. Every participant was subjected to a previously reported structured evaluation process, high-throughput nucleotide sequencing and gene-dosage analysis. Out of 40 individuals with confirmed MODY, 4 (10%) had HNF1B-MODY (harboring either a HNF1B whole-gene deletion or duplication). Postsequencing follow-up biochemical and radiological evaluations revealed the known HNF1B-MODY associated systemic-features, such as transaminitis and structural renal-lesions. These anomalies could have been missed without prior knowledge of the nucleotide-sequencing results. Interestingly, preliminary longitudinal observation (up to 15 years) suggested possibly 2 distinct patterns of renal-deterioration (albuminuric vs. nonalbuminuric chronic kidney disease). Monogenic diabetes like HNF1B-MODY may be missed among young-onset diabetes in a resource-limited routine-care clinic. Collaboration with a MODY-evaluation center may fill the care-gap. The long-term renal-trajectories of HNF1B-MODY will require further studies by dedicated registries and international consortium.