Islet Autoantibodies, Assay Specificity and Disease Specificity

Type 1 Diabetes (T1D) is one of the most common chronic diseases in childhood, which is caused by destruction of insulinproducing pancreatic beta cells. Its incidence increases 3-5% annually and doubles every 20 years [1,2]. On one hand, acute and chronic complications of T1D seriously affect the quality of life and even life span of patients. On the other hand, prognosis can greatly be improved when the disease prediction and closely monitoring are applied, leading to earlier diagnosis and treatment [3]. Islet Autoantibodies (IAbs), as most reliable biomarkers at present for islet autoimmunity, precede clinical T1D by years and play an essential role in prediction and clinical diagnosis of T1D [4,5].

Effects of Calcium Source on Calcium-Metabolic Parameters in Healthy Women and Men

Background/Objectives: Calcium and vitamin D are important for bone health. We compared 24-hour urinary calcium-excretion (Uca/24hrs), during dietary calcium steady-state condition, for different calcium-sources and effects of vitamin D, age and sex. Subjects/Methods: Fifty-two healthy pre- and postmenopausal women and men completed the regimens: placebo, calcium carbonate (400mg) +18μg vitamin D, calcium carbonate (400mg) +38μg vitamin D and 400mg calcium phosphate (milk). Uca/24hrs was measured during dietary calcium steady state as a surrogate measure of calcium-absorption. Serum-calcium, parathyroid hormone (PTH), 25-hydroxy-vitamin D, Procollagen Type 1 N-terminal Pro- Peptide (P1NP) and C-terminal Telopeptide of type 1 collagen (CTX) were measured. Results: Mean daily intake of calcium for the study group ± SD was 1105 ±396 mg. Mean-Uca ± SD: placebo 5.19 ± 2.04 mmol/24hrs, milk 5.88 ± 2.39 mmol/24hrs, (CaCO3+D) 6.19 ± 2.34 mmol/24hrs and (CaCO3 + DD) 6.26 ± 2.32 mmol/day. Uca were higher for all regimens compared to placebo (p <0.001), no difference was found between regimens. CTX was lower during all regimens compared to placebo (p <0.001): placebo 450 ± 243 μg/L, Milk 377 ± 248 μg/L, (CaCO3+D) 392 ± 266 μg/L and (CaCO3+DD) 361 ± 232 μg/L. Conclusions: Uca was higher during supplementation with calcium compared to placebo. Supplementation with calcium reduced bone resorption significantly without effecting PTH. Menopausal status, sex and supplement with vitamin d demonstrated no effect on calcium excretion.

Pheochromocytoma and Takotsubo’s Cardiomyopathy Requiring Extracorporeal Membrane Support: A Report of Two Cases and Review of Takotsubo’s Cardiomyopathy Subtypes

Pheochromocytoma/Paraganglioma (PPGL) are rare neuroendocrine catecholamine secreting tumours that may vary widely in their clinical presentation. Previous case series describe 12% of PPGL patients initially presenting with cardiac complications. Pheochromocytoma-related Takotsubo’s cardiomyopathy has been well described in the literature and may present with primarily basal dyskinesis (inverted subtype), apical dyskinesis (classic subtype), or global dyskinesis. Basal dyskineses has been more commonly described in pheochromocytoma-related Takotsubo’s cardiomyopathy. We present two cases of severe cardiogenic shock requiring Extra-Corporeal Membrane Support (ECMO) with Takotsubo’s cardiomyopathy secondary to pheochromocytoma at University Health Network, Toronto. In both cases, the pheochromocytoma was incidentally discovered on imaging. Both patients responded favourably to ECMO and alpha-adrenergic blockade with recovery of ejection fraction. Both received adrenalectomy as an outpatient with successful recovery. Although rare, PPGL should be considered in younger patients presenting with severe unexplained cardiogenic shock and Takotsubo’s cardiomyopathy.

Raising the Bar When Assessing Cardiovascular Disease Outcome When Studies with Patients with Type 2 Diabetes Mellitus are Constructed: Revisiting ASCEND

The emergence of Type 2 Diabetes Mellitus (T2DM) as a clinical syndrome deviating from rudimentary models including “glucose-insulin” disparities to a clinical syndrome impinged upon hyperactivation of inflammatory-mediated signaling pathways, maladaptive pathophysiological changes, and pleiotropic sequelae has not only changed the nature of discussions regarding diabetes in academic circles, but also the treatment of T2DM clinically. The new challenges faced in preventing the advancement of T2DM coupled with the management of associated chronic disease states have impelled avenues for innovative treatments for T2DM sequelae while also ensuring glycemic control. For example, Sodium-Glucose Transport 2 inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA), in addition to passing mandated Food and Drug Administration (FDA) Cardiovascular Outcome Trials (CVOT), have displayed positive outcomes with respect to cardiorenal considerations in patients with T2DM. Such performances have recently elevated these pleiotropic medications to higher tiers of recommendations by medical societies such as the American Diabetes Association and the American College of Cardiology. Moreover, the tandem of the notion that pleiotropic pharmacotherapeutic options with an expanded understanding of T2DM on the epigenetic, molecular, and cellular domains have galvanized researchers to explore pharmacologic mechanisms in the context of our ever-changing model in T2DM. In this communication, we would like to use lessons from the “Effects of aspirin for primary prevention in persons with diabetes mellitus” (ASCEND) trial to implore aspiring researchers and practitioners to explore, or at least consider external factors of the T2DM patient populous when reporting findings of cardiovascular clinical endpoints for proper context.

The Fluctuation of Serum PTH Level of Type 2 Diabetes mellitus’ Patient on Oral Dapagliflozin

Background: Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors, a set of relatively new medicines treating type 2 diabetes showed a great number of merits in control of glycemia and cardiovascular risk factor management, but also attracted attention on bone fracture. One of those major effects on skeleton might be Parathyroid Hormone (PTH). Case Presentation: We present the case of a 68-year-old female patient with type 2 diabetes on insulin injection and oral acarbose therapy who was admitted with constant hyperglycemia to our hospital. In the beginning, she showed a high level of serum PTH. In the process of oral dapagliflozin treatment, PTH concentration firstly increased and then decreased to the normal range. Diagnostic tests are completed to exclude hyperparathyroidism. Conclusions: The use of SGLT2 inhibitors among diabetes and nondiabetic populations is increasing, a great deal of undiscovered influence, such as hormone and ion fluctuation needs further investigation.

Beyond the Fingerstick: Complications of Diabetes in the Acutely Ill Patient with Covid-19 with Lessons from Translation Biology and Therapeutics

The affliction that the Coronavirus Disease 2019 (COVID-19) pandemic has placed on the infrastructure of healthcare institutions across the globe permeates to the level of the provider, hampering clinical decision-making capacity and capability. Associated with the latter has been unprecedented, sweeping changes in biomedical equipment manufacturing, triage dynamics, and implementation of medical interventions in a landscape replete with clinical literature attempting to characterize features in COVID-19 patients. Preliminary assessments into the elements of the SARS-CoV-2 virus (the strain of coronavirus responsible for COVID-19) in addition to the delineation of patient flux pertaining to COVID-19 has identified diabetes as a prevalent comorbidity with increased mortality and increased disease burden in the acutely ill. The volume of patients with COVID-19 superimposed upon complicated diabetes exemplifies that insight into this association offers an expanded perspective of diabetes mellitus. Moreover, given the extensive organ compromise seen in COVID-19 in addition to the established notion that diabetes is a systemic syndrome of metabolism, an appraisal of the literature of medical management and precursory findings serve as bearings that help render clinical principles into viable treatments. In this review we investigate the array of contemporary literature surrounding COVID-19 with a perspective centered upon the management of acute diabetes complications, namely diabetic ketoacidosis and hyperosmolar hyperglycemic state, with emphases into translational biology and pharmacotherapeutics.

Causes of Hyperprolactinemia in Acromegalic Patients and Clinical Correlations

Hyperprolactinemia in acromegalic patients may result either from cosecretion of growth hormone and prolactin by the tumour or from pituitary stalk compression. The occurrence of both conditions is possible. This study was designed aiming 1) to estimate the prevalence of each cause of hyperprolactinemia and its respective clinical course; 2) to compare the outcomes of patients with tumours staining only for growth hormone against tumours staining for both growth hormone and prolactin. 75 acromegalic patients submitted to transsphenoidal surgery between 1989 and 2018 were included. Patients were divided based on preoperative prolactin levels and immunostaining pattern. Statistical analysis was performed with SPSS version 23. Hyperprolactinemia was documented in 22 out of 36 patients (61%). Stalk compression was the only underlying cause of hyperprolactinemia in 45% of cases. The levels of prolactin were not associated with the immunostaining pattern for prolactin. Clinical differences were not observed between hyperprolactinemic and normoprolactinemic patients, except for a higher frequency of cavernous sinus invasion (64% vs 29%, p=0,064), that reached the level of significance for the subgroup with macroadenomas staining exclusively for growth hormone (p=0,031). In the present series, no clinical differences were noticed between patients with tumours staining only for growth hormone or staining for both growth hormone and prolactin. Hyperprolactinemia resulting from stalk compression is likely to anticipate a less favourable course of disease, since it is associated with larger tumours and a higher frequency of cavernous sinus invasion. On the contrary, positive immunostaining for prolactin was not a marker of worse prognosis.