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

Recruiting

• Conditions: Diabetes Mellitus; NAFLD; Obesity
• Interventions: Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

• Registration Number: NCT06396871
• Lead Sponsor: Technische Universität Dresden

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-16
• Study First Submitted: 2023-12-22
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-29
• Last Update Submitted: 2024-04-29
• Study First Posted: 2024-05-02
• Last Update Posted: 2024-05-02
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
High risk - Liver Fibrosis	Oral glucose tolerance test	1. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa
Low risk - Liver Fibrosis	Liver Ultrasound	Fibroscan measurements \< 8kPa
No Steatotic Liver Disease	Oral glucose tolerance test	No steatosis in liver ultrasound AND CAP ≤ 275 dB/m
Prediabetes	Liver Ultrasound	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
Normal glucose tolerance	Fibroscan of the Liver	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
High risk - Liver Fibrosis	Fibroscan of the Liver	1. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa
Low risk - Liver Fibrosis	Oral glucose tolerance test	Fibroscan measurements \< 8kPa
Low risk - Liver Fibrosis	Fibroscan of the Liver	Fibroscan measurements \< 8kPa
Low risk - Liver Fibrosis	Magentic Resonance Imaging (MRI) of the liver	Fibroscan measurements \< 8kPa
Steatotic Liver Disease	Fibroscan of the Liver	Diagnosis of steatosis in ultrasound AND CAP \> 275 dB/m
No Steatotic Liver Disease	Liver Ultrasound	No steatosis in liver ultrasound AND CAP ≤ 275 dB/m
No Steatotic Liver Disease	Fibroscan of the Liver	No steatosis in liver ultrasound AND CAP ≤ 275 dB/m
No Steatotic Liver Disease	Magentic Resonance Imaging (MRI) of the liver	No steatosis in liver ultrasound AND CAP ≤ 275 dB/m
Normal glucose tolerance	Liver Ultrasound	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
High risk - Liver Fibrosis	Magentic Resonance Imaging (MRI) of the liver	1. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa
Steatotic Liver Disease	Oral glucose tolerance test	Diagnosis of steatosis in ultrasound AND CAP \> 275 dB/m
Diabetes	Fibroscan of the Liver	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
Prediabetes	Oral glucose tolerance test	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
High risk - Liver Fibrosis	Liver Ultrasound	1. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa
Diabetes	Oral glucose tolerance test	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
Diabetes	Liver Ultrasound	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
Diabetes	Magentic Resonance Imaging (MRI) of the liver	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
Normal glucose tolerance	Oral glucose tolerance test	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
Normal glucose tolerance	Magentic Resonance Imaging (MRI) of the liver	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
Steatotic Liver Disease	Liver Ultrasound	Diagnosis of steatosis in ultrasound AND CAP \> 275 dB/m
Steatotic Liver Disease	Magentic Resonance Imaging (MRI) of the liver	Diagnosis of steatosis in ultrasound AND CAP \> 275 dB/m
Prediabetes	Fibroscan of the Liver	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
Prediabetes	Magentic Resonance Imaging (MRI) of the liver	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

Primary Outcome Measures

Name	Time	Method
Qualitative differences in platelets	1 day	% of Platelet aggregation
Quantitative differences in platelets	1 day	Platelet count in GPt/L

Secondary Outcome Measures

Name	Time	Method
Qualitative differences in neutrophils in NETosis	1 day	% of neutrophils performing NETosis (FACS analysis)
Quantitative differences in neutrophils	1 day	Neutrophil count in GPt/L
Quantitative differences in leukocytes	1 day	Leucocyte count in GPt/L
Quantitative differences in lymphocytes	1 day	Lymphocyte count in GPt/L
Qualitative differences in neutrophils in phagocytosis	1 day	% of neutrophils performing phagocytosis (FACS analysis)
Quantitative differences in monocytes	1 day	Monocyte count in GPt/L
Quantitative differences in Interleukin-8	1 day	Interleukin-8 in pg/ml
Qualitative differences in monocytes	1 day	% of monocytes performing phagocytosis (FACS analysis)
Quantitative differences in Interleukin-6	1 day	Interleukin-6 in pg/ml

Trial Locations

Locations (1)

University Study Center for Metabolic Diseases; 🇩🇪 Dresden, Saxony, Germany