Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Completed

CT.gov ID

NCT00829699

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Procedure: euinsulinemic euglycemic glucose clamp Procedure: euinsulinemic hyperglycemic glucose clamp Procedure: Hyperinsulinemic euglycemic glucose clamp Procedure: Hyperinsulinemic hyperglycemic glucose clamp	Early Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus, Question 3

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Euinsulinemic (low insulin infusion) Euglycemic (normal blood glucose levels) glucose clamp with lipid (fat) infusion	Procedure: euinsulinemic euglycemic glucose clamp euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours Other Names: Intralipid
Experimental: 2 Euinsulinemic Hyperglycemic (high glucose levels) glucose clamp with lipid infusion	Procedure: euinsulinemic hyperglycemic glucose clamp euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours Other Names: Intralipid
Experimental: 3 Hyperinsulinemic (High dose insulin) euglycemic glucose clamp with lipid infusion	Procedure: Hyperinsulinemic euglycemic glucose clamp Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours Other Names: Intralipid
Experimental: 4 Hyperinsulinemic hyperglycemic (high glucose level) glucose clamp with lipid infusion	Procedure: Hyperinsulinemic hyperglycemic glucose clamp Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours Other Names: Intralipid

Outcome Measures

Primary Outcome Measures

Percent change in flow mediated dilation of brachial artery [4 hours]

Secondary Outcome Measures

Change in Lipid measures [4hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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:

Medical history/Physical Exam Exclusion Criteria

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