A null mutation in ANGPTL8 does not associate with either plasma glucose or type 2 diabetes in humans.

BACKGROUND: Experiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. However, subsequent experiments in model systems have challenged this proposed role. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes. METHODS: A naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X) is carried by ~1 in 1000 individuals of European ancestry and is associated with higher levels of plasma high-density lipoprotein cholesterol, suggesting that this mutation has functional significance. We examined the association of p.Q121X with fasting glucose levels and risk for type 2 diabetes in up to 95,558 individuals (14,824 type 2 diabetics and 80,734 controls). RESULTS: We found no significant association of p.Q121X with either fasting glucose or type 2 diabetes (p-value = 0.90 and 0.65, respectively). Given our sample sizes, we had >98 % power to detect at least a 0.23 mmol/L effect on plasma glucose and >95 % power to detect a 70 % increase in risk for type 2 diabetes. CONCLUSION: Disruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance.

Isolated shortness of breath in a woman with a history of Hodgkin lymphoma.

BACKGROUND: Isolated shortness of breath in the patient with a history of a malignancy creates a diagnostic challenge and serves as a source of anxiety. Although cancer recurrence is typically the first concern of the patient and the clinician, toxicities of anticancer therapies must also be considered. METHODS: A case of a 49-year-old woman with a distant history of Hodgkin lymphoma with 2 months of progressive dyspnea is presented and discussed. RESULTS: Although the patient was found to have bilateral pleural and pericardial effusions that were concerning for a recurrence of malignancy, analysis and cytology of fluids were negative for cancer. Instead a diagnosis of effusive-constrictive pericarditis secondary to radiation therapy was made. CONCLUSION: When treating a patient with a history of malignancy who presents with dyspnea, it is important to consider the downstream effects related to cancer treatments, even decades later, to guide specific therapies and to assuage the patient's fears.