Type 2 Diabetes
Conditions
Keywords
endothelial function, fibrinolytic balance
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.
Interventions
PROCEDUREeuinsulinemic euglycemic glucose clamp
euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours
PROCEDUREeuinsulinemic hyperglycemic glucose clamp
euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
PROCEDUREHyperinsulinemic hyperglycemic glucose clamp
Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change in flow mediated dilation of brachial artery | 4 hours |
Secondary
| Measure | Time frame |
|---|---|
| Change in Lipid measures | 4hours |
Countries
United States
Outcome results
None listed