Metabolic Phenotyping and Follow-Up of Patients With and Without Diabetes After New Onset of STEMI

Study Overview
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Brief Summary
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The aim of the prospective observational DISTEMI-Study in people with and without Diabetes mellitus (DI) after new onset of ST-Segment Elevation Myocardial Infarction (STEMI) aged 18-80 years at inclusion into the study is to characterize in detail the clinical, metabolical, immunological and vascular phenotype, investigate the interplay between myocardial remodelling and the metabolic phenotype, monitor the progression of the disease and compare the phenotype of STEMI people with diabetes mellitus to people with prediabetes and glucose tolerant people.

Detailed Description
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In detail, the following questions will be answered: Do distinct metabolic phenotypes (with respect to insulin secretion, insulin sensitivity, circulating free fatty acids and ectopic lipid storage, especially in the liver) determine myocardial infarct size and decline of contractile function of the remote myocardium? Which factors modify the progression of the disease (insulin resistance, ectopic lipid storage, subclinical inflammation, abnormal energy metabolism)? People are thoroughly examined at baseline and one year after STEMI. Can we identify risk profiles and their relevance for development of diabetes-associated complications as well as long-term progression of diabetes? Can we improve risk assessment algorithms for targeted therapy in line with Precision Medicine?

Official Title
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Metabolic Phenotyping and Follow-Up of Patients With and Without Diabetes Mellitus After New Onset of ST-Segment Elevation Myocardial Infarction (STEMI) (DISTEMI Study)

Conditions
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ST-segment Elevation Myocardial Infarction (STEMI), Diabetes Mellitus, Insulin Resistance, Non-Alcoholic Fatty Liver Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Condition after new onset of ST-segment elevation myocardial infarction (STEMI) Age 18-80 years HbA1c <9.0% People with diagnosis of diabetes mellitus according to ADA and DDG criteria (i.e. HbA1c ≥6.5% and/or pathological oral glucose tolerance test) Healthy people with normal glucose tolerance status according to ADA and DDG criteria (i.e. HbA1c <5.7% and normal OGTT) People with impaired glucose metabolism (prediabetes) according to ADA and DDG criteria (i.e. impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4%) Consent-able, hemodynamically stable people, without sedation (e.g. opiates) or other interfering medication (e.g. catecholamines) Exclusion Criteria: Diabetes mellitus category 3 A-H (ADA criteria), gestational diabetes Current pregnancy Infectious diseases, acute infections / fever Immunosuppressive therapy Severe chronic renal, liver or heart disease (e.g. serum creatinin ≥1.6 mg/dl, peripheral artery occlusive disease stage IV) Malignant diseases Severe chronic psychiatric illness or addiction Participation in an intervention trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort with type 1 diabetes (T1D) and type 2 diabetes (T2D)<br>Prospectively followed cohort of people with new onset of ST-segment elevation myocardial infarction and diabetes mellitus (type 1 or type 2) according to the American Diabetes Association (ADA) and German Diabetes Society (DDG) criteria (HbA1c ≥6.5% or pathological oral glucose tolerance test (OGTT)), aged 18-80 years at inclusion into the study | |
| Cohort of normal glucose tolerant people (NGT)<br>Prospectively followed cohort of healthy people with new onset of ST-elevation myocardial infarction and normal glucose tolerance status (HbA1c <5.7% and normal OGTT), aged 18-80 years at inclusion into the study | |
| Cohort of people with impaired glucose metabolism (IGM)<br>Prospectively followed cohort of people with new onset of ST-elevation myocardial infarction and impaired glucose metabolism, usually called prediabetes including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and/or HbA1c 5.7-6.4%, aged 18-80 years at inclusion into the study | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of cardiac function | Measurement of left-ventricular ejection fraction by cardiac magnetic resonance (MR) imaging | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of insulin sensitivity (M-Value) | Measurement of whole body insulin sensitivity with hyperinsulinemic euglycemic clamp (HEC) | One year | 
| Change of insulin secretion | Measurement of beta-cell function with oral and intravenous glucose tolerance test | One year | 
| Change of ectopic fat distribution | Measurement of cardiac and hepatic lipid content by MR spectroscopy (MRS) | One year | 
| Change of liver stiffness | Measurement of liver stiffness by transient elastography (Fibroscan®) and MR elastography (MRE) | One year | 
| Change of energy metabolism | Measurement of myocardial and hepatic phosphocreatine(PCr)-to-adenosine triphosphate(ATP) Ratio by MRS | One year | 
| Change of mitochondrial respiratory function | Measurement of lymphocyte mitochondrial respiration by Oxygraph-O2k | One year | 
| Change of Fatty liver index | Estimate calculated by laboratory and anthropometric parameters for assessment of liver steatosis | One year | 
| Change of Homeostasis Model Assessment 2 Estimate | HOMA2-IR is calculated by laboratory and anthropometric parameters for non-invasive assessment of insulin sensitivity under fasted condition | One year | 
| Incidence of further cardiovascular diseases (CVD) and STEMI-related complications, new onset of prediabetes and diabetes mellitus and associated comorbidities | Determination of the prevalence of cardiovascular diseases and associated complications (i.e. heart failure, recurrent infarction, morbidity, mortality), new onset of prediabetes and diabetes, diabetes-related complications and associated comorbidities | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ST-segment elevation myocardial infarction, STEMI, Cardiovascular diseases, CVD, Diabetes mellitus, Normal glucose tolerance, Non-alcoholic fatty liver disease, NAFLD, Liver fibrosis