Effects of COVID-19 Infection on Beta-cell Function in Euglycemic Patients
Condition: COVID19; BETA-CELL FUNCTION
MeSH terms: COVID-19
Study type: Interventional

Summary: 
      In recent months, a new coronavirus, SARS-CoV-2, has been identified as the cause of a
      serious lung infection named COVID-19 by the World Health Organization. This virus has spread
      rapidly among the nations of the world and it is the cause of a pandemic and a global health
      emergency. There is still very little scientific evidence on the virus, however
      epidemiological data suggest that one of the most frequent comorbidities is diabetes, along
      with hypertension and heart disease. There is no scientific evidence on the possible effects
      of this infection on the function of the β cell and on glycemic control. Clinical evidence
      seems to suggest that COVID-19 infection mostly affects the respiratory system, and an acute
      worsening of glycemic compensation is not described as generally observed in bacterial
      pneumonia. However, previous work on acute respiratory syndromes (SARS) caused by similar
      coronaviruses, had described that the infection has multi-organ involvement related to the
      expression of the SARS coronavirus receptor, the angiotensin 2 converting enzyme, in
      different organs, especially at the level of endocrine pancreatic tissue. In the population
      of this previous work, glucose intolerance and fasting hyperglycaemia have been described and
      in 37 of 39 diabetic patients examined, a remission of diabetes was observed three years
      after the infection. It is possible that the coronaviruses responsible for SARS may enter the
      pancreatic islets using the angiotensin 2 converting enzyme receptor, expressed at the level
      of the endocrine pancreas, thus causing diabetes. Additionally, previous literature on
      coronavirus infections (SARS and MERS or Middle-East Respiratory Syndrome) suggested that
      diabetes could worsen the evolution of the disease. In particular, in case of Middle-East
      Respiratory Syndrome-CoV infection, diabetic mice had a more prolonged serious illness and a
      delay in recovery regardless of the viremic titer. This could probably be due to a
      dysregulation of the immune response, which results in more serious and prolonged lung
      disease.

      There are currently no data on pancreatic beta cell function in patients with COVID-19.
    

Detailed description: 
      The project is monocentric, interventional, non-pharmacological, non-profit. Patients will be
      enrolled in hospital for confirmed COVID-19 infection (with reverse transcriptase-polymerase
      chain reaction on the airway swab) but with normal basal blood glucose and no previous
      history of diabetes or impaired fasting glucose or impaired glucose tolerance. Patients will
      be compared to a control group of healthy volunteers, not affected by COVID-19 and with no
      previous history of diabetes or impaired fasting glucose or impaired glucose tolerance.
      Patients will be also compared with a group of patients with type 2 diabetes but without
      COVID-19. Once the informed consent has been signed, the clinical parameters and biochemical
      parameters will be collected according to the time points provided by the protocol in
      positive COVID-19 patients, in healthy volunteers and in patients with type 2 diabetes.

      COVID-19 positive patients and healthy controls as well as patients with type 2 diabetes,
      will undergo a stimulation test of β-cell function (evaluation of the secretive response of
      insulin to the stimulation test with arginine infusion) and the monitoring of glycemic values
      through a professional retrospective continuous glucose monitoring. For the test, an infusion
      solution containing 25% arginine hydrochloride will be used, arginine is an insulinogenic
      amino acid, useful to verify the possible existence of damage to the cellular beta function
      induced by COVID-19 infection, clinically observable with changes in insulin secretory
      response. Given the usefulness of the test, performed for diagnostic purposes, this protocol
      is identified as "non-pharmacological". The test is contraindicated only in patients with
      severe hepatic and renal insufficiency, in all other subjects the side effects are minimal
      and spontaneous resolution before the end of the test (flushing 33%, oral paraesthesia 46%,
      nausea 12%, dizziness 14%). For the stimulation test with arginine infusion, after the basal
      sampling at (0 minutes), an intravenous injection of arginine 5 grams will be practiced in 60
      seconds followed by serial withdrawals at +2, +5, +10 and +30 minutes. The following analytes
      will be assayed on the basal sample: glycosylated hemoglobin, glycaemia, insulin,
      pro-insulin, C-peptide, glucagon, serum inflammatory cytokines (Il1β, IL-2, IL-6, IL-7,
      IL-10, TNF- α, IFN-γ, MIP-1β, MCP-1, GM-CSF, G-CSF Insulin, C-peptide and glucagon will be
      dosed on all points of the curve.
    

Intervention name(s): Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection
Intervention type(s): Diagnostic Test
Intervention description(s): All participants will be subjected to the collection of glycemic data through continuous professional retrospective monitoring of blood glucose for seven days, positioned on the day the test will be performed. During the entire recording period, parameters such as mean glucose, estimated glycosylated hemoglobin, peak glucose and nadir, blood sugar levels above the limit of 140 mg / dL, average glucose values at 60 and 120 minutes after meals, standard deviation and variability coefficient.
The evaluation of insulin secretion will be evaluated by performing the stimulus test with arginine infusion according to validated protocols.
Other intervention name(s): Positioning of the device for glycemic monitoring
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic