Deep Phenotyping of Peripheral Blood Cells and Circulating Factors in Metabolic Diseases (PERIMED)

Technische Universität Dresden

Status: Enrolling

Conditions: Diabetes Mellitus; Obesity; NAFLD

Treatments: Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver; Diagnostic Test: Liver Ultrasound

Study type: Observational

Funder types: Other

Identifiers

NCT06396871

BO-EK-508112022

Details and patient eligibility

About

The goal of this cross-sectional observational study is to to perform a thorough characterization of the quantitative and qualitative differences in peripheral blood cells, and circulating factors (proteins, metabolites, lipids, extracellular vesicles) in different stages of several metabolic diseases (diabetes, obesity, non-alcoholic fatty liver disease) that share common pathophysiological mechanisms and in comparison with adult healthy controls. The main question[s] it aims to answer are:

• Which are the quantitative (number and concentration) and qualtitative (characteristics, functional assays) differences in platelets in patients with metabolic diseases vs subjects without metabolic diseases
• Which are the quantitative (number and concentration) and qualtitative (characteristics, functional assays) differences in leucocytes or circulating molecules in patients with metabolic diseases vs subjects without metabolic diseases

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Age > 18 years old

Additional inclusion criteria for case groups:

1. High risk group for significant liver fibrosis

   1. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa

2. Steatotic Liver Disease group

   1. Diagnosis of steatosis in ultrasound AND CAP > 275 dB/m

3. Prediabetes

   1. HbA1c >5.7 AND <6.5% OR/AND
   2. Fasting Glucose 100-125 mg/dl OR/AND
   3. Glucose at 120 min of OGTT between 140-200 mg/dl

4. Diabetes 1. HbA1c ≥ 6.5% OR/AND 2. Fasting Glucose > 126 mg/dl OR/AND 3. Glucose at 120 min of OGTT > 200 mg/dl

   If a subject does not fulfil the additional criteria for participating in a case group, then he/she will be included in the respective control group which will be:

   A#) Low risk for significant liver fibrosis 1. Fibroscan measurements < 8kPa B#) No steatosis group

   1. No steatosis in liver ultrasound AND CAP ≤ 275 dB/m C#) Normal glucose tolerance test group
   2. HbA1c < 5.7% AND
   3. Fasting glucose < 100 mg/dl AND
   4. Glucose at 120 min of OGTT <140 mg/dl

   Exclusion Criteria:

   1. Diabetes mellitus Typ 1
   2. BMI < 18.5 kg/m2
   3. Transfusion of blood or major bleeding in the last six months
   4. Anaemia with haemoglobin < 9,0 g/dl
   5. Chronic alcohol or drug abuse
   6. Presence of any acute or chronic liver disease apart from non-alcoholic fatty liver disease (i.e. viral, autoimmune or alcoholic hepatitis, haemochromatosis, Morbus Wilson etc.)
   7. Systemic infections (CRP > 1 mg/dl)
   8. Medications that affect blood glucose levels (e.g. antidiabetics [except from the subjects forming the diabetes group], steroids) in the last six months
   9. Medications that affect coagulation (e.g. anticoagulants and antiplatelet agents) in the last six months
   10. Medications that affect immune function (e.g. immunosuppressive drugs) in the last six months
   11. Pregnancy or breastfeeding
   12. Severe psychic disorders
   13. Inability to follow the study protocol
   14. Have any medical condition unsuitable for inclusion in the study, in the opinion of the investigator

   Additional exclusion criteria for MRI:

   1. Pacemaker
   2. Artificial heart valve
   3. Metal prosthesis
   4. Implanted magnetic metal parts
   5. Spirals
   6. Fixed metal dental braces
   7. Acupuncture needle
   8. Insulin pumps
   9. By MRI > 3 Tesla: Tattoos, permanent eyeliner
   10. Claustrophobia or any other condition, such as psychiatric disorder, that in the opinion of the investigator may prevent the participant from following and completing the protocol
   11. Subject dimensions not allowing the performance of MRI

Trial design

180 participants in 7 patient groups

High risk - Liver Fibrosis

Description:

1. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa

Treatment:

Diagnostic Test: Oral glucose tolerance test

Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diagnostic Test: Liver Ultrasound

Diagnostic Test: Fibroscan of the Liver

Low risk - Liver Fibrosis

Description:

Fibroscan measurements \< 8kPa

Treatment:

Diagnostic Test: Oral glucose tolerance test

Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diagnostic Test: Liver Ultrasound

Diagnostic Test: Fibroscan of the Liver

Steatotic Liver Disease

Description:

Diagnosis of steatosis in ultrasound AND CAP \> 275 dB/m

Treatment:

Diagnostic Test: Oral glucose tolerance test

Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diagnostic Test: Liver Ultrasound

Diagnostic Test: Fibroscan of the Liver

No Steatotic Liver Disease

Description:

No steatosis in liver ultrasound AND CAP ≤ 275 dB/m

Treatment:

Diagnostic Test: Oral glucose tolerance test

Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diagnostic Test: Liver Ultrasound

Diagnostic Test: Fibroscan of the Liver

Diabetes

Description:

1. HbA1c ≥ 6.5% OR/AND 2. Fasting Glucose \> 126 mg/dl OR/AND 3. Glucose at 120 min of OGTT \> 200 mg/dl AND/OR history of Diabetes, treated with at least one antidiabetic medication

Treatment:

Diagnostic Test: Oral glucose tolerance test

Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diagnostic Test: Liver Ultrasound

Diagnostic Test: Fibroscan of the Liver

Prediabetes

Description:

1. HbA1c \>5.7 AND \<6.5% OR/AND 2. Fasting Glucose 100-125 mg/dl OR/AND 3. Glucose at 120 min of OGTT between 140-200 mg/dl

Treatment:

Diagnostic Test: Oral glucose tolerance test

Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diagnostic Test: Liver Ultrasound

Diagnostic Test: Fibroscan of the Liver

Normal glucose tolerance

Description:

1. HbA1c \< 5.7% AND 2. Fasting glucose \< 100 mg/dl AND 3. Glucose at 120 min of OGTT \<140 mg/dl and no history of Diabetes

Treatment:

Diagnostic Test: Oral glucose tolerance test

Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diagnostic Test: Liver Ultrasound

Diagnostic Test: Fibroscan of the Liver