Effects of SARS-CoV-2 Infection on Beta-cell Function in Euglycemic Patients

University of Milan1 site in 1 country90 target enrollmentStarted: June 30, 2020Last updated: May 10, 2023

Conditions

Interventions

Trial Snapshot

Phase: Not Applicable
Status: Completed
Sponsor: University of Milan
Enrollment: 90
Locations: 1
Primary Endpoint: Serum β - cellular function index insulin levels

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

Brief 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.

Study Design

Study Type: Interventional
Allocation: Non Randomized
Intervention Model: Crossover
Primary Purpose: Diagnostic
Masking: None

Eligibility Criteria

Ages: 18 Years to 80 Years (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: Yes

Inclusion Criteria

•for COVID-19 positive patients
•Male and female patients with COVID19 and normal basal blood sugar, unprecedented in diabetes or impaired fasting glucose or impaired glucose tolerance
•Age> 18 years and <80 years
•Availability to informed consent and corporate privacy
•Inclusion criteria for healthy subjects
•Male and female patients not affected by COVID19, unprecedented in diabetes or impaired fasting glucose or impaired glucose tolerance
•Age> 18 years and <80 years
•Availability to informed consent and corporate privacy

Exclusion Criteria

•for COVID-19 positive patients
•Age <18 years
•Previous history of diabetes or impaired fasting glucose or impaired glucose tolerance
•Severe liver failure
•Severe kidney failure
•Exclusion criteria for healthy subjects
•Age <18 years
•Previous history of diabetes or impaired fasting glucose or impaired glucose tolerance
•Positivity to the nasopharyngeal swab for SARS-CoV-2
•Severe liver failure
•Severe kidney failure
•Inclusion criteria for T2D patients
•Male and female patients not affected by COVID19 with a diagnosis of type 2 diabetes
•Age> 18 years and <80 years
•Availability to informed consent and corporate privacy
•Exclusion criteria for T2D patients
•Age <18 years
•Positivity to the nasopharyngeal swab for SARS-CoV-2
•Severe liver failure
•Severe kidney failure

Arms & Interventions

COVID-19 positive patients

Experimental

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 glucose and no previous history of diabetes or impaired fasting glucose or impaired tolerance glucose. Patients will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. 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.

Intervention: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection (Diagnostic Test)

Healthy volunteers

Other

Healthy volunteers, not affected by COVID-19 and with no previous history of diabetes or impaired fasting glucose or impaired glucose tolerance will be enrolled. Healthy volunteers will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. 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.

Intervention: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection (Diagnostic Test)

Type 2 diabetes patients

Other

Patients with established Type 2 diabetes, not affects by COVID-19. Patients will be placed with a professional retrospective glucose monitoring device and will be tested for stimulation with arginine infusion. The device will be placed on the day of the test and will be removed after seven days of recording the glycemic data. 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.

Intervention: Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection (Diagnostic Test)