Consequences of Hypoglycaemia on Cardiovascular and Inflammatory Responses

Diabetes Mellitus, Type 2 Clinical Trial

— HCIR  

Official title:

Consequences of Hypoglycaemia on Cardiovascular and Inflammatory Responses in Patients With Diabetes Mellitus Type 1, Type 2 and Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03976271
• Other study ID #: HCIR
• Status: Completed
• Phase: N/A
• Start date: August 12, 2019
• Est. completion date: March 31, 2021

Study information

• Verified date: March 2021
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

People with Type 1 diabetes (T1DM), type 2 diabetes (T2DM) and healthy volunteers will undergo a hypoglycaemic clamp to to investigate the effect of hypoglycaemia on cardiovascular and inflammatory responses.

Description:

Objectives: The overall aim of the present study is to investigate the effect of hypoglycaemia on cardiovascular and inflammatory responses, molecular mechanisms and epigenetic profiles in various groups of people with diabetes type 1, type 2 and healthy volunteers.

Study design: Intervention study

Intervention: All subjects will undergo a hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (nadir 2.8 mmol/L), during and after which blood and urine will be sampled for further examination for up to one week.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Overall inclusion criteria

• Ability to provide written informed consent

• Must be able to speak and read Danish (for Hillerød-site) and Dutch (for Nijmegen-site)

• Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump) (except for group 5)

• Body-Mass Index: 19-40 kg/m2

• Age =18 years, = 80 years

• Blood pressure: <140/90 mmHg

• Duration of diabetes > 1 year (except for group 5)

• HbA1c < 100 mmol/mol

Group specific

• Group 1: HbA1c >64 mmol/mol

• Group 2: impaired awareness of hypoglycaemia (IAH) as assessed by a score of =3 on the modified Clarke questionnaire, =4 on the Gold questionnaire and a positive score on the Pedersen-Bjergaard questionnaire.

• Group 3: normal awareness of hypoglycaemia (NAH) as assessed by a score of <3 on the modified Clarke questionnaire, <4 on the Gold questionnaire and a negative score on the Pedersen-Bjergaard.

• Group 4: Insulin treatment for at least 1 year

• Group 5/6: HbA1c <42 mmol/mol

Exclusion Criteria:

• - Severe medical or psychological conditions interfering with the perception of hypoglycaemia other than IAH such as brain injuries, epilepsy, a major cardiovascular disease event or anxiety disorders

• Use of immune-modifying drugs or antibiotics

• Treatment with glucose-modifying (other than insulin, SGLT-2 inhibitors and metformin) agents (e.g. prednisolon)

• Use of anti-depressive drugs

• Pregnancy or breastfeeding or unwillingness to undertake measures for birth control

• Use of statins (e.g. stop statins >2 weeks before performing blood sampling. This can be safely done in the context of primary prevention)

• Any event of cardiovascular disease in the past 5 years (e.g. myocardial infarction, stroke, heart failure, symptomatic peripheral arterial disease)

• Auto-inflammatory or auto-immune diseases

• Any infection in past three months

• Previous vaccination in the past three months

• Laser coagulation for proliferative retinopathy in the past six months

• Proliferative retinopathy

• Diabetic nephropathy as reflected by an albumin-creatinine ratio ? 30 mg/gor an estimated glomerular filtration rate (by MDRD) ?60ml/min/1.73m2

• History of pancreatitis (acute or chronic) or pancreatic cancer

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Hypoglycemia
• Inflammatory Response

Intervention

Procedure:
• hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp
For this study, a hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp will be conducted to investigate the effect of hypoglycaemia. This means that subjects will receive an intravenous insulin infusion, at a continuous rate of 60 mU·m-2·min-1, as well as glucose 20% w/w intravenously at a variable rate, adjusted by arterial plasma glucose levels, measured at 5 minute intervals.

Locations

Country	Name	City	State
Denmark	Nordsjællands University Hospital	Hillerød	Nordsjaelland
Netherlands	Radboudumc	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Rigshospitalet, Denmark

Countries where clinical trial is conducted

Denmark,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inflammatory responses of hypoglycaemia by measuring the cytokine production of isolated monocytes using ELISA	Cytokine production (TNF-alfa, IL-6, IL-10 and IL-1ß) of isolated and stimulated monocytes	1.5 year
Secondary	Atherogenic responses of (recurrent) hypoglycaemia using foam cell formation.	Measurement of Ox-LDL uptake by measuring intracellular apolipoproteine B	1.5 year
Secondary	Metabolomics profile of each group	Un-targeted metabolomics and identification of metabolites based on exact mass using metabolomics library	1.5 year
Secondary	Epigenetic modifications	Epigenetic modifications due to hypoglycaemia in the promoter regions of the pro-inflammatory cytokines in monocytes	1.5 year
Secondary	Cardiac function responses to hypoglycaemia using echocardiography	Cardiac function responses to hypoglycaemia using echocardiography	1.5 year
Secondary	Cognitive function responses to hypoglycaemia using cognitive function tests (TAP, PASAT)	Amount of correct answers	1.5 year
Secondary	Oxidative stress responses using oxidative stress marker	Excretion of guanine nucleosides in urine (ng/mL)	1.5 year