Triglyceride Clearance in Hypertriglyceridemic Pancreatitis: Time Course and Its Implications for Management.

Objective: To characterize the time course of triglyceride (Tg) lowering in hypertriglyceridemic (HTg) pancreatitis according to the initial Tg values, causes, and interventions.

Methods: Patients hospitalized from October 2013 through December of 2018 with a diagnosis of pancreatitis associated with HTg (Tg level, ≥500 mg/dL), in the absence of other causes, were identified by medical record review. Tg lowering was retrospectively assessed for differences in relation to the initial Tg values, use of intravenous insulin, ethanol-associated versus nonethanol-associated causes, and time to Tg values of <500 versus <1000 mg/dL.

Development and Resolution of Secondary Adrenal Insufficiency after an Intra-Articular Steroid Injection.

Corticosteroid injections are commonly indicated in inflammatory conditions involving the soft tissues, tendon sheaths, bursae, and joints. Local corticosteroids carry a lower risk of complications than systemic corticosteroid but may be systemically absorbed and subsequently suppress the hypothalamic-pituitary-adrenal (HPA) axis. This can cause secondary adrenal insufficiency (SAI) as well as iatrogenic Cushing's syndrome.

Spontaneous Adrenal Hemorrhage with Mild Hypoadrenalism in a Patient Anticoagulated with Apixaban for Antiphospholipid Syndrome: A Case Report and Literature Review.

Background: Adrenal hemorrhage (AH) is a serious endocrine complication of antiphospholipid syndrome (APLS). . We report a 45-year-old man who presented with several deep venous thromboses and was initially treated with apixaban, who later developed bilateral AH.

A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH.

Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by mild elevations in serum calcium and relatively low urinary calcium excretion. It results from an elevated set point in serum calcium arising from variants in the calcium-sensing receptor (CaSR) gene but also AP2S1 and GNA11 genes, which encode for adaptor-related protein complex 2 and G11 proteins, respectively. The manifestations of FHH can vary and sometimes overlap with primary hyperparathyroidism making the diagnosis challenging.

Fournier's Gangrene and Diabetic Ketoacidosis Associated with Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Life-Threatening Complications.

BACKGROUND Sodium glucose co-transporter 2 (SGLT2) inhibitors have become an appealing treatment for diabetes due to their favorable cardiac and renal outcomes. However, reports continue to emerge describing potentially life-threatening adverse events such as Fournier's gangrene and diabetic ketoacidosis associated with their use. Herein, we present a case of simultaneous Fournier's gangrene and diabetic ketoacidosis after initiation of treatment with canagliflozin.

Hyperparathyroidism-Jaw Tumor Syndrome Associated With Large-Scale 1q31 Deletion.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant cause of familial hyperparathyroidism associated with benign, ossifying fibromas of the maxillofacial bones and increased risk of parathyroid carcinoma. The putative tumor suppressor gene has been implicated in the syndrome, with a multitude of inactivating mutations identified; however, HPT-JT due to large-scale deletion of the chromosomal region containing the gene is exceedingly rare, and the clinical significance of this variant remains unclear. We report the case of a 32-year-old woman with a history of mandibular ossifying fibroma who presented with primary hyperparathyroidism and was found to harbor a large-scale, germline deletion on chromosome 1q31, including the locus.

Current Therapies for the Medical Management of Diabetes.

Diabetes affects a large and diverse number of individuals who share in common its risks for complications but who differ greatly from one another in age, health, and a number of circumstances influential to successful treatment. Because type 2 diabetes comprises the majority of diabetes cases, a number of agents have been developed for its treatment. Their unique properties offer opportunities to overcome some of the treatment limitations of older medicines and enable a more individualized and flexible approach to glucose-lowering.

Second-generation antisense oligonucleotides against β-catenin protect mice against diet-induced hepatic steatosis and hepatic and peripheral insulin resistance.

Although mutations in the Wnt/β-catenin signaling pathway are linked with the metabolic syndrome and type 2 diabetes in humans, the mechanism is unclear. High-fat-fed male C57BL/6 mice were treated for 4 wk with a 2'-O-methoxyethyl chimeric antisense oligonucleotide (ASO) to decrease hepatic and adipose expression of β-catenin. β-Catenin mRNA decreased by ≈80% in the liver and by 70% in white adipose tissue relative to control ASO-treated mice.

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids.

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance--wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-(13)C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently.

Targeting pyruvate carboxylase reduces gluconeogenesis and adiposity and improves insulin resistance.

We measured the mRNA and protein expression of the key gluconeogenic enzymes in human liver biopsy specimens and found that only hepatic pyruvate carboxylase protein levels related strongly with glycemia. We assessed the role of pyruvate carboxylase in regulating glucose and lipid metabolism in rats through a loss-of-function approach using a specific antisense oligonucleotide (ASO) to decrease expression predominantly in liver and adipose tissue. Pyruvate carboxylase ASO reduced plasma glucose concentrations and the rate of endogenous glucose production in vivo.

Investigational anti-hyperglycemic agents: the future of type 2 diabetes therapy?

As the pandemic of type 2 diabetes spreads globally, clinicians face many challenges in treating an increasingly diverse patient population varying in age, comorbidities, and socioeconomic status. Current therapies for type 2 diabetes are often unable to alter the natural course of the disease and provide durable glycemic control, and side effects in the context of individual patient characteristics often limit treatment choices. This often results in the progression to insulin use and complex regimens that are difficult to maintain.

Role of patatin-like phospholipase domain-containing 3 on lipid-induced hepatic steatosis and insulin resistance in rats.

Unlabelled: Genome-wide array studies have associated the patatin-like phospholipase domain-containing 3 (PNPLA3) gene polymorphisms with hepatic steatosis. However, it is unclear whether PNPLA3 functions as a lipase or a lipogenic enzyme and whether PNPLA3 is involved in the pathogenesis of hepatic insulin resistance. To address these questions we treated high-fat-fed rats with specific antisense oligonucleotides to decrease hepatic and adipose pnpla3 expression.