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

Inclusion criteria

• Age > 18 years old

Additional inclusion criteria for case groups:

• High risk group for significant liver fibrosis

• FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa
• Steatotic Liver Disease group

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

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

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

Exclusion criteria

• Diabetes mellitus Typ 1
• BMI < 18.5 kg/m2
• Transfusion of blood or major bleeding in the last six months
• Anaemia with haemoglobin < 9,0 g/dl
• Chronic alcohol or drug abuse
• 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.)
• Systemic infections (CRP > 1 mg/dl)
• Medications that affect blood glucose levels (e.g. antidiabetics [except from the subjects forming the diabetes group], steroids) in the last six months
• Medications that affect coagulation (e.g. anticoagulants and antiplatelet agents) in the last six months
• Medications that affect immune function (e.g. immunosuppressive drugs) in the last six months
• Pregnancy or breastfeeding
• Severe psychic disorders
• Inability to follow the study protocol
• Have any medical condition unsuitable for inclusion in the study, in the opinion of the investigator

Additional exclusion criteria for MRI:

• Pacemaker
• Artificial heart valve
• Metal prosthesis
• Implanted magnetic metal parts
• Spirals
• Fixed metal dental braces
• Acupuncture needle
• Insulin pumps
• By MRI > 3 Tesla: Tattoos, permanent eyeliner
• 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
• Subject dimensions not allowing the performance of MRI