Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus

NCT ID: NCT00829699

Last Updated: 2019-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2014-04-30

Brief Summary

The purpose of this study is to learn more about why patients with diabetes have increased heart attacks, strokes and other illnesses due to blood clots causing blockage of a blood vessel. The proposed protocol will study the separate and combined effects of high glucose and high fats on certain cardiovascular responses in Type 2 DM.

Detailed Description

Currently 75-80% of diabetes mellitus (DM) patients die due to thrombotic causes. Data from the Centers for Disease Control and Prevention released in 2000 indicated that mortality due to coronary artery disease is decreasing except in individuals with diabetes. Clearly the disordered metabolism, which includes abnormal metabolism of fats resulting in higher triglyceride and free fatty acid blood levels, occurring in diabetes predisposes these individuals to increased thrombotic events. Unless the underlying mechanisms responsible for these events can be identified, there will be an unprecedented number of diabetic patients suffering thrombotic episodes in the next 10 years.

The specific aims of this study are to determine the effects of elevated free fatty acids and hyperglycemia (high glucose)on endothelial function and thrombolytic balance in patients with type 2 diabetes, and to determine the effects of increased insulin in this setting.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

1

Euinsulinemic (low insulin infusion) Euglycemic (normal blood glucose levels) glucose clamp with lipid (fat) infusion

Group Type: EXPERIMENTAL

euinsulinemic euglycemic glucose clamp

Intervention Type: PROCEDURE

euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours

2

Euinsulinemic Hyperglycemic (high glucose levels) glucose clamp with lipid infusion

Group Type: EXPERIMENTAL

euinsulinemic hyperglycemic glucose clamp

Intervention Type: PROCEDURE

euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

3

Hyperinsulinemic (High dose insulin) euglycemic glucose clamp with lipid infusion

Group Type: EXPERIMENTAL

Hyperinsulinemic euglycemic glucose clamp

Intervention Type: PROCEDURE

Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

4

Hyperinsulinemic hyperglycemic (high glucose level) glucose clamp with lipid infusion

Group Type: EXPERIMENTAL

Hyperinsulinemic hyperglycemic glucose clamp

Intervention Type: PROCEDURE

Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

Interventions

euinsulinemic euglycemic glucose clamp

euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours

Intervention Type: PROCEDURE

euinsulinemic hyperglycemic glucose clamp

euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

Intervention Type: PROCEDURE

Hyperinsulinemic euglycemic glucose clamp

Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

Intervention Type: PROCEDURE

Hyperinsulinemic hyperglycemic glucose clamp

Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

Intervention Type: PROCEDURE

Other Intervention Names

Intralipid; Intralipid; Intralipid; Intralipid

Eligibility Criteria

Inclusion Criteria

• 16 Type 2 diabetic patients age 18 - 60 yrs
• 16 Non-diabetic controls age 18-60 yrs
• Body mass index >20 kg/m2
• Female volunteers of childbearing potential: negative urine pregnancy test
• Volunteers over 40 years old: an ECG with no clinically significant conduction or ischemic changes.
• For those with type 2 diabetes: HBA1C > 5.5%
• For those with type 2 diabetes: C-peptide >0.2 nmol, If C-peptide is abnormal or there is a clinical suspicion for type 1 diabetes, MODY or LADA, anti-islet cell and anti-GAD antibodies will be assessed to establish the diagnosis of type 2 diabetes vs. type 1/LADA/MODY.
• PT (time) 12.8-14.6 seconds, PTT (time) 25-38 seconds

Exclusion Criteria

• Any current disease condition that alters carbohydrate metabolism (other than type 2 DM) and/or evidence for clinically significant cardiac disease
• Uncontrolled hypertension
• Pregnancy
• Subjects unable to give voluntary informed consent
• Subjects with history of pancreatitis
• Subjects on anticoagulant drugs, anemic, or with known bleeding diseases
• Subjects with history of GI bleeding requiring treatment
• Tobacco Use
• Subjects with history of heparin-induced thrombocytopenia or heparin allergy
• Subjects with severe egg or legume (soybean) allergy
• Abnormal results following screening tests and physical examination that is clinically significant:

• Fever greater than 38 degrees C at screening or study initiation
• Uncontrolled severe hypertension (i.e., blood pressure greater than 160/100)
• Cardiac Abnormalities (e.g. Heart Failure, Arrhythmia, Cardiomyopathy, ischemic tachycardia, S-T segment deviations, etc.,) from history or ECG testing in subjects > 40 years old.
• Diagnosed Pneumonia
• Hepatic Failure/Jaundice
• Clinically significant coagulopathy
• Renal Failure
• Acute Cerebrovascular/ Neurological deficit

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Stephen N. Davis, MBBS

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen N. Davis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

Univerisity of Maryland, Baltimore

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

RFAHL04016

Identifier Type: -

Identifier Source: secondary_id

HP-00044874

Identifier Type: -

Identifier Source: org_study_id