RESUMO
A 46-year-old woman was type 1 diabetes diagnosed at the age of 9 who had previously been on an insulin pump. Other co-morbidities included CKD IV, HTN, and hypothyroidism. She presented with hyperglycemia of 400 mg/dl and fluid retention. Her GFR had decreased to 13. Her physical exam was notable for respiratory distress and anasarca. She failed to respond to aggressive IV diuresis and urgent hemodialysis was initiated. The patient had been lost to outpatient follow-up for a year. She had been co-managed by an endocrinologist and a primary care physician but had stopped going to her endocrinologist over a year ago due to inability to afford the co-pays. She subsequently lost her insurance and had to pay out of pocket for her insulin; at this point, she decided to stop seeing her PCP and began to ration her insulin. Due to social stigma, she did not mention her financial issues to her healthcare providers. After identifying these challenges, we decided to start her on a more affordable regimen of NPH insulin. Through social work assistance, we were able to obtain a charity hemodialysis chair and discharge her home. She applied to Medicaid. Healthcare expenditure with regard to diabetes rose to $327 billion from $245 billion in 2012. The price of insulin has continued to increase even after the drug's patent has expired due to the combination of FDA requirements, a monopoly in the insulin market, and the lack of federal price controls and Pharmacy Benefits Managers. The high out of pocket costs for insulin has led to many instances of insulin rationing among both uninsured and insured. This led to death in some cases as well as poorly controlled diabetes with increased complications and mortality as in our case. We present a case report and narrative review on insulin affordability.
RESUMO
Chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) affects an estimated 35 million and 75 million individuals worldwide, respectively. These viruses induce persistent inflammation which often drives the development or progression of organ-specific diseases and even cancer including Hepatocellular Carcinoma (HCC). In this study, we sought to examine inflammatory responses following HIV or HCV stimulation of macrophages or Kupffer cells (KCs), that may contribute to virus mediated inflammation and subsequent liver disease. KCs are liver-resident macrophages and reports have provided evidence that HIV can stimulate and infect them. In order to characterize HIV-intrinsic innate immune responses that may occur in the liver, we performed microarray analyses on KCs following HIV stimulation. Our data demonstrate that KCs upregulate several innate immune signaling pathways involved in inflammation, myeloid cell maturation, stellate cell activation, and Triggering Receptor Expressed on Myeloid cells 1 (TREM1) signaling. TREM1 is a member of the immunoglobulin superfamily of receptors and it is reported to be involved in systemic inflammatory responses due to its ability to amplify activation of host defense signaling pathways. Our data demonstrate that stimulation of KCs with HIV or HCV induces the upregulation of TREM1. Additionally, HIV viral proteins can upregulate expression of TREM1 mRNA through NF-кB signaling. Furthermore, activation of the TREM1 signaling pathway, with a targeted agonist, increased HIV or HCV-mediated inflammatory responses in macrophages due to enhanced activation of the ERK1/2 signaling cascade. Silencing TREM1 dampened inflammatory immune responses elicited by HIV or HCV stimulation. Finally, HIV and HCV infected patients exhibit higher expression and frequency of TREM1 and CD68 positive cells. Taken together, TREM1 induction by HIV contributes to chronic inflammation in the liver and targeting TREM1 signaling may be a therapeutic option to minimize HIV induced chronic inflammation.
