Rinkoo Dalan

An Unusual Outbreak of Hypoglycemia

Between January 1 and May 26, 2008, a total of 150 nondiabetic patients with severe hypoglycemia were admitted to the five public hospitals in Singapore. On specific questioning, 45 patients (30%) admitted ingesting illegal sexual-enhancement drugs before the onset of hypoglycemia.

Pituitary apoplexy associated with cabergoline therapy

Pituitary apoplexy is a rare medical emergency which results from hemorrhage or infarction in the pituitary gland. One of the predisposing factors is treatment with dopamine agonists, especially bromocriptine. We report a 20-year-old Chinese man with prolactinoma who developed pituitary apoplexy 6 weeks after initiation of cabergoline. He was treated conservatively with supportive therapy, and recovered well with no loss of pituitary function. A literature search was conducted and a review of the reported patients with pituitary apoplexy during treatment with dopamine agonists is discussed.

Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus.

Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 μL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings.

High-sensitivity C-reactive protein concentrations among patients with and without diabetes in a multiethnic population of Singapore: CREDENCE Study

Objectives To determine whether high-sensitivity C-reactive protein (hs-CRP) concentrations differ between Chinese, Malays, and Indians with and without type 2 diabetes mellitus and to look for an association with demographic, metabolic and therapeutic variables. Methods Phase 1: We retrieved records of 50 Chinese, 51 Malay, and 67 Indian individuals who had routine health screening blood tests. Phase 2: We recruited 111 Chinese, 68 Malays, and 67 Indians with type 2 diabetes mellitus and measured their hs-CRP in addition to standard laboratory tests. Results Phase 1: The median hs-CRP was 0.6 mg/L (0.2–6.2) in Chinese, 1.2 mg/L (0.2–7.9) in Malays, and 1.9 mg/L (0.2–10.0) in Indians. The Indians had higher hs-CRP compared to Chinese (P < 0.05) when adjusted for age, sex, body mass index (BMI), lipids, blood pressure, and smoking, and a significant correlation was seen between female sex, smoking status, fasting glucose and triglyceride concentration, and hs-CRP in all three ethnicities. Phase 2: The median hs-CRP was 1.2 mg/L (0.2–9.9) in Chinese, 2.2 mg/L (0.2–9.0) in Malays, and 2.3 mg/L (0.2–9.8) in Indians. Indians had higher hs-CRP when compared to Chinese (P < 0.05) and a significant correlation was seen between BMI, female gender, diabetes, and the use of metformin and hs-CRP in all three ethnicities (P < 0.05) when adjusted for the above variables and use of aspirin, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACE-I/ARB), statin, metformin, rosiglitazone, sulfonylurea, glinides, acarbose, and insulin. Conclusion hs-CRP concentrations are significantly higher in Indians compared to the Chinese (in both the diabetic and nondiabetic individuals) after adjustment for the various demographic, metabolic, and therapeutic variables.

A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial

We sought to determine if vitamin D supplementation, to target 25(OH)D concentrations of 30–40 ng/mL, improves endothelial function in Singapore’s multi-ethnic type 2 diabetes mellitus population. We randomised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [baseline 25(OH)D < 20 ng/mL] or cholecalciferol 2000 International Unit/matching placebo [baseline 25(OH)D: 20–30 ng/mL] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry (reactive hyperaemia index–endothelial peripheral arterial tonometry) and vascular biomarkers: E-selectin, von-Willebrand factor and high-sensitivity C-reactive protein. We compared the change from baseline parameters in the two groups using Student’s t-test or Kruskal–Wallis test. A log-normal multivariate regression analysis was used to adjust for relevant baseline variables. The median reactive hyperaemia index in the vitamin D group increased from 0.65 (interquartile range: 0.42) to 0.73 (interquartile range: 0.36), whereas it decreased from 0.73 (interquartile range: 0.65) to 0.65 (interquartile range: 0.38) (p = 0.02) in the placebo group. After adjustment for baseline variables, the change was not statistically significant for reactive hyperaemia index (p = 0.07) and for other vascular biomarkers (p > 0.05). Targeted vitamin D supplementation for 16 weeks resulted in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort.

MULTIPLE ENDOCRINOPATHIES ASSOCIATED WITH LITHIUM THERAPY

OBJECTIVE To illustrate a case of lithium-associated primary hyperparathyroidism, thyrotoxicosis, and nephrogenic diabetes insipidus and to discuss the potential mechanisms for these complications. METHODS We describe the clinical and laboratory findings in our current patient and review the related medical literature. RESULTS A 65-year-old Chinese woman with bipolar affective disorder, who had received maintenance lithium therapy for 10 years, was seen in an acute care hospital because of fever and confusion. Investigations showed that she had primary hyperparathyroidism and hyperthyroidism. She underwent a parathyroidectomy, which revealed a parathyroid adenoma. Her initial subclinical hyperthyroidism evolved into overt hyperthyroidism after use of lithium was discontinued. Therapy was initiated with carbimazole, which was up-titrated briefly; the patient was subsequently weaned off this medication. Her postoperative course was complicated by persistent polyuria in conjunction with a negative fluid balance, consistent with nephrogenic diabetes insipidus. Thus, amiloride therapy was instituted. The results of an objective causality assessment suggested that the primary hyperparathyroidism, hyperthyroidism, and nephrogenic diabetes insipidus were possibly or probably related to the lithium therapy. CONCLUSION Lithium remains an intriguing drug with numerous potential endocrinologic complications. It is important that clinicians prescribing lithium are aware of its side effects and have a strategy for their detection and management.

Latent tuberculosis in patients with diabetes mellitus: prevalence, progression and public health implications.

BACKGROUND Diabetes mellitus (DM) confers a higher risk for tuberculosis (TB). Yet, TB screening and chemoprophylaxis for latent TB infection (LTBI) in DM remains controversial. We conducted a cross-sectional study to elucidate LTBI prevalence and longitudinal follow-up to ascertain LTBI to active TB progression rate in DM. METHODS 220 DM patients without previous TB from the outpatient diabetes clinic of the hospital were enrolled. T-Spot TB, tuberculin-skin-test (TST) and chest radiography (CXR) were performed. LTBI was defined by negative CXR with reactive T-Spot TB. Progression to active TB was confirmed by cross-checking against the TB registry. RESULTS The prevalence of LTBI was 28.2% (62/220) by reactive T-Spot. None progressed to active TB from 2007-2013. Multivariate analysis revealed that any co-morbidity (p=0.016) was positively associated while metformin (p=0.008) was negatively associated with LTBI. CONCLUSIONS Over a quarter of DM patients harbor LTBI. While the lack of demonstrable progression to active TB within the follow-up time frame up to this point does not unequivocally support a routine TB screening policy or anti-TB chemoprophylaxis for LTBI in a diabetic population for now, this preliminary evidence needs re-evaluation with longer follow-up of this enrolled cohort over the next decade.

Neuroglycopenia and adrenergic responses to hypoglycaemia: insights from a local epidemic of serendipitous massive overdose of glibenclamide.

Aims  Recently, an unlicensed aphrodisiac formulation originating from China known as ‘Power 1 Walnut’ penetrated the illicit markets of South East Asia including Singapore. Subsequent toxicological analyses revealed that each ‘Power 1 Walnut’ pill was illegally adulterated with two prescription drugs—sildenafil 1 mg (a PDE5 inhibitor) and glibenclamide 93–98 mg (a long‐acting sulphonylurea). As the drug was peddled to numerous people, a local ‘hypoglycaemia epidemic’ ensued, of which a small cluster presented to our hospital with severe hypoglycaemia. The aim is to characterize the demographics, clinical and labouratory aspects and postulate mechanisms for the relatively atypical presentation.

Ethnic variation in the correlation between fasting glucose concentration and glycated hemoglobin (HbA1c).

OBJECTIVE We aimed to determine the relationship between fasting serum glucose (FSG) concentration and glycated hemoglobin-A1c (HbA1c) in the 3 ethnicities in Singapore after adjustment for demographic and therapeutic variables. METHODS Fasting serum glucose (FSG), HbA1c, and serum creatinine levels were simultaneously sampled from 575 patients with diabetes (389 Chinese, 97 Indians, 89 Malays) in this cross-sectional study between January and May 2008, and the results were subjected to multivariate linear regression analysis. RESULTS We found a significant interaction between FSG and ethnicity on HbA1c. The correlation between FSG and HbA1c among Chinese subjects was 0.25 (95% confidence interval [CI]:0.2-0.3) relative to the Malays (0.38, 95% CI: 0.30-0.45) after adjustment for age; gender; serum creatinine concentrations; body mass index (BMI); duration of diabetes; use of sulfonylureas, metformin, and insulin; and hemoglobin (Hb) and red cell indices (P = .005). Hence, for a given FSG, the predicted HbA1c will be higher in Malays compared to Chinese subjects. We did not observe a statistically significant difference between Indians and Malays with respect to the correlation between FSG and HbA1c. CONCLUSION We showed a higher correlation between HbA1c and FSG in Malay subjects relative to the Chinese in this cohort. The ethnic variation in the HbA1c-FSG relationship may be related to differences in percentage contribution by the FSG to overall HbA1c among ethnic groups. Future studies using continuous glucose monitoring (CGM) to elucidate the relative contributions by FSG and postprandial glucose (PPG) to the daily blood glucose profile and the overall HbA1c by ethnicity are required.

Pre-operative Serum Alkaline Phosphatase as a Predictor for Hypocalcemia Post-Parathyroid Adenectomy

Background. Post-operative hypocalcemia (POH) may complicate parathyroidectomy for primary hyperparathyroidism. This study investigates the relationship between POH and pre-operative risk factors to identify a simple method to predict POH risk. Methods. Retrospective data on risk factors for 29 patients was collected for age, pre-operative serum calcium, alkaline phosphatase (ALP), parathyroid hormone (PTH), adenoma size, gender, and bisphosphonate pre-treatment. These were screened to exclude those with small effect sizes, and analyzed using Univariate General Linear Modeling (GLM) with trough serum calcium (TSC) as the dependent variable. The regression function of the significant variables against TSC was plotted with 95% CI fit lines. The cut-off regression value was read from the lower fit line for the threshold TSC of 2.0 mmol/L. Results. After screening, log-transformed age (r=0.600), ALP (r=-0.415), and PTH (r=-0.433) were entered into GLM analysis, which showed that only ALP was significant (p=0.016 Eta-squared=0.220). The GLM model had a partial Eta-squared of 0.559 with 98% observed power. The plot of TSC against log-ALP gave an ALP cut-off of 340 U/L. Conclusions. The study shows that there is a strong relationship between ALP and TSC, and that patients with a pre-operative ALP less than 340 U/L are unlikely to have symptomatic POH (100% sensitivity, 95% specificity). While vitamin D was not analyzed in this study, the ALP cut-off is conservative and should still screen out cases with severe vitamin D deficiency. We therefore recommend that pre-operative ALP be utilized to complement clinical protocols for POH management in parathyroid adenomectomy patients.