Consequences of Hypoglycaemia on Cardiovascular and Inflammatory Responses (HCIR)

Radboud University Medical Center

Status: Completed

Conditions: Hypoglycemia; Diabetes Mellitus, Type 1; Inflammatory Response; Diabetes Mellitus, Type 2

Treatments: Procedure: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Study type: Interventional

Funder types: Other

Identifiers

NCT03976271

HCIR

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

110 participants in 6 patient groups

T1DM poor glycaemic control

Active Comparator group

Description:

patients with type 1 diabetes and poor glycaemic control (HbA1c \>8% / \>64 mmol/mol will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Treatment:

Procedure: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

T1DM impaired awareness

Active Comparator group

Description:

patients with type 1 diabetes and impaired awareness of hypoglycaemia will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Treatment:

Procedure: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

T1DM Normal awareness

Active Comparator group

Description:

patients with type 1 diabetes and normal awareness of hypoglycaemia will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Treatment:

Procedure: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

T2DM + Insulin

Active Comparator group

Description:

patients with type 2 diabetes with insulin treatment for at least 1 year will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Treatment:

Procedure: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Healthy control T2DM

Active Comparator group

Description:

healthy controls without diabetes and age, gender and BMI matched with diabetes type 2 participants will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Treatment:

Procedure: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Healthy control T1DM

Active Comparator group

Description:

Healthy controls without diabetes and age, gender and BMI matched with diabetes type 1 participants will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp

Treatment:

Procedure: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp