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

Обзор

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

Вмешательства

• Диагностический тест Oral glucose tolerance test
  75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min
• Диагностический тест Liver Ultrasound
  A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.
• Диагностический тест Fibroscan of the Liver
  FibroScan non-invasively measures the stiffness of the liver by capturing and calculating the speed of a shear wave as it travels through the liver (vibration controlled transient elastography).
• Диагностический тест Magentic Resonance Imaging (MRI) of the liver
  The exact calculation of liver fat with proton density fat fraction will take place with MRI.

Первичные конечные точки

• Qualitative differences in platelets [Срок оценки: 1 day]
• Quantitative differences in platelets [Срок оценки: 1 day]

Вторичные конечные точки (9)

• Quantitative differences in leukocytes [Срок оценки: 1 day]
• Quantitative differences in neutrophils [Срок оценки: 1 day]
• Quantitative differences in lymphocytes [Срок оценки: 1 day]
• Quantitative differences in monocytes [Срок оценки: 1 day]
• Qualitative differences in neutrophils in NETosis [Срок оценки: 1 day]
• Qualitative differences in neutrophils in phagocytosis [Срок оценки: 1 day]
• Qualitative differences in monocytes [Срок оценки: 1 day]
• Quantitative differences in Interleukin-6 [Срок оценки: 1 day]
• Quantitative differences in Interleukin-8 [Срок оценки: 1 day]

Критерии участия

Критерии включения

1\. Age > 18 years old

Additional inclusion criteria for case groups:

• High risk group for significant liver fibrosis

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

• Steatotic Liver Disease group

1\. 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

1\. 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Германия · 1 центр

• University Study Center for Metabolic Diseases — Dresden

Идентификаторы

NCT: NCT06396871 · BO-EK-508112022

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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