Effects of COVID-19 Infection on Beta-cell Function in Euglycemic Patients

NCT04463849 | Completed

• 1 other identifier: 6/2020
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID19; BETA-CELL FUNCTION

Outcome Measures

Primary Outcomes (6)

• Serum β - cellular function index insulin levels

  Difference in insulin levels during and after COVID-19 infection and compared to patients in the control group

  all data were collected at Visit 1, 12 months

• Serum β - cellular function index C-peptide levels

  Difference in C-peptide levels during and after COVID-19 infection and compared to patients in the control group

  all data were collected at Visit 1, 12 months

• Serum β - cellular function HOMA-β index

  Difference in HOMA-β index during and after COVID-19 infection and compared to patients in the control group

  all data were collected at Visit 1, 12 months

• Serum β - cellular function pro-insulin/insulin ratio

  Difference in pro-insulin/insulin ratio during and after COVID-19 infection and compared to patients in the control group

  all data were collected at Visit 1, 12 months

• Evaluation of the secretory response of insulin to the arginine stimulation test

  Check for the existence of damage to the beta cell function induced by COVID-19 infection, clinically observable with changes in the secretory response of insulin

  all data were collected at Visit 1, 12 months

• Percentage of patients with preserved β cells function

  Evidence of impairment of β cell function in the serum of COVID-19 patients

  all data were collected at Visit 1, 12 months

Secondary Outcomes (13)

• Glucose values

  all data were collected at Visit 1, 12 months

• Values of continuous glucose monitoring

  all data were collected at Visit 1 and after 7 days, 12 months

• Changes in the inflammatory marker interleukin 1-β

  all data were collected at Visit 1, 12 months

• Changes in the inflammatory marker interleukin IL-2

  all data were collected at Visit 1, 12 months

• Changes in the inflammatory marker interleukin IL-6

  all data were collected at Visit 1, 12 months

Study Arms (3)

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.

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

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.

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

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.

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

Interventions

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

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.

Also known as: Positioning of the device for glycemic monitoring

COVID-19 positive patients; Healthy volunteers; Type 2 diabetes patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• Age \<18 years
• Previous history of diabetes or impaired fasting glucose or impaired glucose tolerance
• Severe liver failure
• Severe kidney failure
• 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
• 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
• Age \<18 years
• Positivity to the nasopharyngeal swab for SARS-CoV-2
• Severe liver failure

Sponsors & Collaborators

• University of Milan: lead
• Luigi Sacco University Hospital: collaborator

Study Sites (1)

Sacco University Hospital

Milan, MI, 20157, Italy

Location

Related Publications (8)

• Deng SQ, Peng HJ. Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China. J Clin Med. 2020 Feb 20;9(2):575. doi: 10.3390/jcm9020575.

  PMID: 32093211 BACKGROUND

• Kulcsar KA, Coleman CM, Beck SE, Frieman MB. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI Insight. 2019 Oct 17;4(20):e131774. doi: 10.1172/jci.insight.131774.

  PMID: 31550243 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010 Sep;47(3):193-9. doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31.

  PMID: 19333547 BACKGROUND

• Shankar SS, Vella A, Raymond RH, Staten MA, Calle RA, Bergman RN, Cao C, Chen D, Cobelli C, Dalla Man C, Deeg M, Dong JQ, Lee DS, Polidori D, Robertson RP, Ruetten H, Stefanovski D, Vassileva MT, Weir GC, Fryburg DA; Foundation for the National Institutes of Health beta-Cell Project Team. Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of beta-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series. Diabetes Care. 2016 Sep;39(9):1602-13. doi: 10.2337/dc15-0931. Epub 2016 Jul 12.

  PMID: 27407117 BACKGROUND

• Brandle M, Lehmann R, Maly FE, Schmid C, Spinas GA. Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNA(LEU(UUR)) gene mutation. Diabetes Care. 2001 Jul;24(7):1253-8. doi: 10.2337/diacare.24.7.1253.

  PMID: 11423511 BACKGROUND

• Bolla AM, Loretelli C, Montefusco L, Finzi G, Abdi R, Ben Nasr M, Lunati ME, Pastore I, Bonventre JV, Nebuloni M, Rusconi S, Santus P, Zuccotti G, Galli M, D'Addio F, Fiorina P. Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19. Diabetes Metab Res Rev. 2022 Oct;38(7):e3565. doi: 10.1002/dmrr.3565. Epub 2022 Jul 22.

  PMID: 35830597 DERIVED

• Ben Nasr M, D'Addio F, Montefusco L, Usuelli V, Loretelli C, Rossi A, Pastore I, Abdelsalam A, Maestroni A, Dell'Acqua M, Ippolito E, Assi E, Seelam AJ, Fiorina RM, Chebat E, Morpurgo P, Lunati ME, Bolla AM, Abdi R, Bonventre JV, Rusconi S, Riva A, Corradi D, Santus P, Clark P, Nebuloni M, Baldi G, Finzi G, Folli F, Zuccotti GV, Galli M, Herold KC, Fiorina P. Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets. Diabetes. 2022 Jul 1;71(7):1579-1590. doi: 10.2337/db21-0926.

  PMID: 35499468 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 9, 2020
• Study Start: June 30, 2020
• Primary Completion: October 31, 2021
• Study Completion: December 31, 2021
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)