A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019.

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro . Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m 2 , and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).

Type 2 diabetes mellitus in Peru: A literature review including studies at high-altitude settings.

We performed a comprehensive review of recent publications about type 2 diabetes mellitus (T2DM) in Peru, including studies among people living at high altitude above the sea level. An increase in the prevalence of T2DM in Peru has been reported, the reasons are multifactorial and coinciding with the strong economic growth that our country has experienced over the last 20 years along with migration from the Andean regions to the coast and the adoption of a lifestyle that is a known to be a risk factor for obesity and insulin resistance. Scarce information is available in Peru about the prevalence of chronic complications of T2DM such as retinopathy, neuropathy, and nephropathy. There is a need for a health care plan based on early diagnosis of T2DM to reduce social and economic problems, as recommended by the WHO and the United Nations.

Type B Insulin Resistance in Peru.

Type B insulin resistance (IR) is a rare autoimmune disease characterized by the presence of insulin receptor autoantibodies, resulting in a marked IR inducing hyperglycemia. Our first case is a 42-year-old female with a history of RA, SLE and Hashimoto-thyroiditis that presented with cachexia, acanthosis-nigricans, hirsutism, negative anti-insulin-ab and glucose level between 400 to 700 mg/dl, despite a total insulin dose of 1000 IU/day. She received pulses of cyclophosphamide along with prednisone. One year later the patient was off insulin and with HbA1c of 5.6%. The second case is a 42-year-old female patient that presented with polyuria, polydipsia, cachexia, acanthosis-nigricans, negative glutamic-acid-decarboxilase-ab and positive TPO-ab. She received IV infusion of regular insulin at a rate of 500 UI/d. Two years later she was off insulin with HbA1C of 5.6%. As summary, we reported a case of a disease remitted after receiving immunosuppressive therapy and a case of disease remitted spontaneously.