Fulminant type 1 diabetes, an underrecognized and unique subtype of type 1 diabetes: A case series from Singapore.

Fulminant type 1 diabetes (FT1D) is a unique subtype of type 1 diabetes, characterized by acute absolute insulin deficiency, severe ketosis, and increased risk of hypoglycemia, glycemic variability and microvascular complications. Seven people with FT1D were identified from two tertiary centers in Singapore. Six were Chinese, the mean age was 35 years and all were lean (mean body mass index 20.3 kg/m2 ). All presented with diabetes ketosis or ketoacidosis and low C-peptide. All but one had low glutamic acid decarboxylase antibodies. Nearly half had a missed/delayed diagnosis of FT1D. Three had frequent hypoglycemia, which improved after transition to continuous subcutaneous insulin infusion therapy. Individuals with FT1D experience unique diagnostic and management challenges associated with rapid absolute insulin deficiency. Greater awareness about this clinical entity is required.

Expanding the use of salivary cortisol as a non-invasive outpatient test in the dynamic evaluation of suspected adrenal insufficiency.

Background: Adrenal insufficiency (AI) is potentially life-threatening, and accurate diagnosis is crucial. The first-line diagnostic test, the adrenocorticotrophic hormone (ACTH) stimulation test, measures serum total cortisol. However, this is affected in states of altered albumin or cortisol-binding globulin levels, limiting reliability. Salivary cortisol reflects free bioactive cortisol levels and is a promising alternative. However, few studies are available, and heterogenous methodologies limit applicability. Methods: This study prospectively recruited 42 outpatients undergoing evaluation for AI, excluding participants with altered cortisol-binding states. Serum (immunoassay) and salivary (liquid chromatography tandem mass spectrometry) cortisol levels were sampled at baseline, 30 min, and 60 min following 250 µg synacthen administration. AI was defined as a peak serum cortisol level <500 nmol/L in accordance with guidelines. Results: The study recruited 21 (50%) participants with AI and 21 without AI. There were no significant differences in baseline characteristics, blood pressure, or sodium levels between groups. Following synacthen stimulation, serum and salivary cortisol levels showed good correlation at all timepoints (R2 = 0.74, P < 0.001), at peak levels (R2 = 0.72, P < 0.001), and at 60 min (R2 = 0.72, P < 0.001). A salivary cortisol cut-off of 16.0 nmol/L had a sensitivity of 90.5% and a specificity of 76.2% for the diagnosis of AI. Conclusion: This study demonstrates a good correlation between serum and salivary cortisol levels during the 250 µg synacthen test. A peak salivary cortisol cut-off of 16.0 nmol/L can be used for the diagnosis of AI. It is a less invasive alternative to evaluate patients with suspected AI. Its potential utility in the diagnosis of AI in patients with altered cortisol-binding states should be further studied.

Bariatric Surgery in Kidney Transplant Candidates and Recipients: Experience at an Asian Center.

Background: Kidney transplant (KT) candidates and recipients with obesity experience more frequent complications such as infection, poorer allograft outcomes, diabetes, and mortality, limiting their eligibility for transplantation. Bariatric surgery (BS) is not commonly performed among KT patients given concerns about immunosuppression absorption, wound healing, infections, and graft outcomes. Its role has not been described before in an Asian KT patient setting. Methods: A retrospective review of patients who underwent BS at the largest KT center in Singapore from 2008 to 2020 was conducted. Metabolic outcomes, immunosuppression doses, graft outcomes, and mortality were studied. Results: Seven patients underwent BS and KT (4 underwent BS before KT, 3 underwent BS after KT; 4 underwent sleeve gastrectomy, 3 underwent gastric bypass). Mean total weight losses of 23.8% at 1 year and 18.6% at 5 years post-BS were achieved. Among the five patients with diabetes, glycemic control improved after BS. There were no deaths in the first 90 days or graft loss in the first year after KT and BS. Patients who underwent BS after KT had no significant changes in immunosuppression dose. Conclusion: BS can be safely performed in KT recipients and candidates and results in sustainable weight losses and improvements in metabolic comorbidities. Although no major complications were observed in our study, close monitoring of this complex group of patients is imperative.

High Urinary Sodium Concentrations in Severe SIADH: Case Reports of 2 Patients and Literature Review.

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 <30 mmol/L is highly suggestive of hypovolemic hyponatremia and good response to saline infusion, there is lack of clarity of the threshold of which high urine sodium concentration can differentiate various causes of natriuresis such as SIADH, renal or cerebral salt wasting. Apart from high urine osmolality (>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.

Acute Flaccid Tetraparesis after COVID-19 Infection: Think of the Thyroid.

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 ß-blockers, antithyroid medications, and intravenous potassium chloride (KCl). Despite frequent monitoring of potassium, rebound hyperkalaemia occurred with prompt resolution of paralysis.

Centile Charts for Monitoring of Weight Loss Trajectories After Bariatric Surgery in Asian Patients.

BACKGROUND: Following bariatric surgery, accurate charting of weight loss and regain is crucial. Various preoperative factors affect postoperative weight loss, including age, sex, ethnicity, and surgical type. These are not considered by current weight loss metrics, limiting comparison of weight loss outcomes between patients or centers and across time. METHODS: Patients (n=1022) who underwent sleeve gastrectomy (n=809) and gastric bypass (n=213) from 2008 to 2020 in a single center were reviewed. Weight loss outcomes (% total weight loss) were measured for 60 months postoperatively. Longitudinal centile lines were plotted using the post-estimation predictions of quantile regression models, adjusted for type of procedure, sex, ethnicity, and baseline BMI. RESULTS: Median regression showed that %TWL was 1.0% greater among males than females (ß = +1.1, 95% CI: +0.6 to +1.7, P = <0.0001). Participants who underwent SG had less %TWL compared to GB (ß = -1.3, 95% CI: -1.9 to -0.8, P < 0.0001). There was a trend towards less %TWL among the Indian and Malay participants compared to Chinese. Age and diabetes were not significant predictors. Reference centile charts were produced for the overall cohort, as well as specific charts adjusted for type of bariatric procedure, sex, ethnicity, and baseline BMI. CONCLUSION: Centile charts provide a clinically relevant method for monitoring of weight trajectories postoperatively and aid in realistic and personalised goal setting, and the early identification of "poor responders". This is the first study to present post-bariatric surgery centile charts for an Asian cohort.

Hypertriglyceridemia-induced pancreatitis in pregnancy: case review on the role of therapeutic plasma exchange.

SUMMARY: Gestational hypertriglyceridemia-induced pancreatitis is associated with significant maternal and fetal morbidity and mortality. We report a case of gestational hypertriglyceridemia-induced pancreatitis in a primigravida at 31-weeks gestation, complicated by impending preterm labor and metabolic acidosis requiring hemodialysis. This was successfully managed with therapeutic plasma exchange (TPE), followed by i.v. insulin, low-fat diet, and omega-3. Triglyceride levels stabilized after TPE and the patient underwent an uncomplicated term delivery. In pregnancy, elevated estrogen and insulin resistance exacerbate hypertriglyceridemia. Management is challenging as risks and benefits of treatment options need to be weighed against fetal wellbeing. We discuss management options including a review of previous case reports detailing TPE use, dietary optimization, and delivery timing. This case emphasizes the importance of multidisciplinary care to optimize maternal and fetal outcomes. LEARNING POINTS: Gestational hypertriglyceridemia-induced pancreatitis has high morbidity. A multidisciplinary team approach is a key as maternal and fetal needs must be addressed. Rapid lowering of triglycerides is crucial and can be achieved successfully and safely with plasma exchange. A low-fat diet while ensuring adequate nutrition in pregnancy is important. Timing of delivery requires consideration of fetal maturity and risk of recurrent pancreatitis.

The Impact of Bariatric Surgery Compared to Medical Therapy on Health-Related Quality of Life in Subjects with Obesity and Type 2 Diabetes Mellitus.

INTRODUCTION: The adverse implications of obesity extend beyond physical health to include negative impact on quality of life (QoL), mood, and eating habits. While bariatric surgery provides successful weight loss and metabolic benefits, studies describe conflicting results on QoL and mood-related outcomes. METHODS: Patients (n = 140) with class II/III obesity and T2DM were recruited from 2015 to 2019, and stratified based on medical or surgical treatment. Questionnaires including the Hospital Anxiety and Depression Scale, Euro QoL visual analogue scale (EQ-VAS), and Revised 21-item Three-Factor Eating Questionnaire (TFEQ-R21) were recorded at baseline, 6 months, and 12 months after treatment. RESULTS: At baseline, the surgical group (n = 55) and medical group (n = 85) had no significant difference in questionnaire outcomes. At 6 and 12 months, EQ-VAS was higher in the surgical group (12 months surgical 82.00 ± 12.64, medical 72.81 ± 16.56, p = 0.001), with greater improvement from baseline. HADS-D scores at 12 months were lower in the surgical group (surgical 2.60 ± 2.88, medical 3.90 ± 3.58, p = 0.025). At 12 months, the surgical group also had better TFEQ-R21 scores, with higher cognitive restraint scores (surgical 19.09 ± 3.00, medical 16.69 ± 3.61, p < 0.001), and lower scores for uncontrolled eating (surgical 14.96 ± 3.87, medical 17.89 ± 5.34, p = 0.001). CONCLUSION: In the treatment of patients with obesity and T2DM, bariatric surgery resulted in improved QoL outcomes at 12 months compared to medical therapy. This could be related to improvement in weight and metabolic outcomes, and altered gut-brain axis communication. This is the first prospective study assessing the impact of bariatric surgery on health-related QoL in Asia compared against a control group who received medical therapy.

Bilateral Aldosterone Suppression in Patients With Right Unilateral Primary Aldosteronism and Review of the Literature.

INTRODUCTION: Adrenal vein sampling (AVS) identifies unilateral primary aldosteronism but may occasionally show paradoxically low aldosterone-cortisol ratios bilaterally. Postulated reasons include venous anomalies, fluctuating aldosterone secretion, or superselective cannulation. We report our findings in patients who underwent repeat AVS and reviewed the current literature. METHODS: We performed a retrospective observational study of patients undergoing AVS in an experienced high-volume tertiary center over a 5-year period. RESULTS: From 2015 to 2019, 61 patients underwent sequential cosyntropin-stimulated AVS and all had bilateral successful cannulation (100%). Four of 61 (6.6%) patients had bilaterally low aldosterone-cortisol ratios. Three patients underwent repeat AVS, with all 3 cases demonstrating right-sided lateralization and cure of disease postadrenalectomy. Right-sided disease was also more common in other reports. This may be due to inadvertent superselective cannulation of the short right adrenal vein, resulting in sampling of the adjacent normal gland. Cortisol results cannot detect this problem. In 1 patient, computed tomography venography excluded any accessory right adrenal veins. In another patient, repeat bilateral simultaneous unstimulated AVS was done, and measurements of metanephrines aided in accurately identifying right-sided lateralization. CONCLUSION: In addition to technical difficulties in cannulating the right adrenal vein, we also have to avoid performing superselective cannulation inadvertently. In cases of inconclusive AVS, repeat sampling may identify patients with potentially curable unilateral primary aldosteronism. The role of corticotropin stimulation and metanephrines measurements during repeat AVS requires further study.

Preoperative Weight Loss via Very Low Caloric Diet (VLCD) and Its Effect on Outcomes After Bariatric Surgery.

INTRODUCTION: The effect of preoperative weight loss via very low caloric diet (VLCD) on long-term weight loss post-bariatric surgery (BS) is conflicting. We analysed its impact on weight loss and other outcomes post-BS. METHODS: Patients (n = 306) who underwent sleeve gastrectomy or gastric bypass from 2008 to 2018 were studied. VLCD was prescribed for 14 days preoperatively. Patients were followed up for 5 years. Postoperative weight loss was compared in patients with preoperative weight gain or weight loss < 5% (WL < 5%), and weight loss ≥ 5% (WL ≥ 5%). Preoperative WL compared weight before and after VLCD; postoperative WL compared post-VLCD weight and follow-up weight. Total weight loss (TWL) encompassed pre- and postoperative WL. RESULTS: WL was < 5% in 87.3% and ≥ 5% in 12.7%. There was no significant difference in complication rate, duration of surgery or length of stay, regardless of surgical type. Patients with WL < 5% lost more weight postoperatively compared with WL ≥ 5% for up to 60 months (%postoperative WL at 1 month: WL < 5% = 13.7%, WL ≥ 5% = 10%, p = <0.001; 60 months: WL < 5% = 30.6%, WL ≥ 5% = 23.9%, p = 0.041). However, when TWL and percentage of excess body mass index loss (%EBMIL) were measured, there was no difference beyond 6 months. A predictive multivariable model for 1-year %EBMIL was formed. Significant variables included pre-VLCD BMI and preoperative WL, and the relationship between the two. CONCLUSION: Preoperative WL via VLCD was associated with reduced postoperative WL after BS, with no significant effect on complications, long-term TWL or %EBMIL. This challenges the notion that preoperative WL via VLCD should be mandated for better postoperative outcomes.