Metabolic Causes of Thrombosis in Type 2 Diabetes - Question 4

SCCOR in Hemostatic and Thrombotic Diseases Project 5 - Metabolic Causes of Thrombosis in Type 2 Diabetes

Hypoglycemia (low blood glucose level) occurs frequently in intensively treated patients with diabetes. Although hypoglycemia was thought to occur almost exclusively in T1DM, with the advent of improved metabolic control in T2DM, the incidence of hypoglycemia is rising in these patients. Therefore in this application, we will test the novel hypothesis that prior hypoglycemia will result in (cardiovascular complications) during subsequent hypoglycemia.

This study will test the hypothesis that 1) hypoglycemia causes a prothrombotic state and defective endothelial function and 2) episodes of repeated hypoglycemia will result in greater impairments of endothelial function and an increased prothrombotic tendency. Preliminary data in healthy men demonstrates that hypoglycemia can dramatically increase PAI-1 levels and the PAI-1 to tPA ratio, thereby creating a prothrombotic state. Whether this also occurs in type 2 DM patients is unknown. Furthermore, the effects of hypoglycemia on endothelial function in T2DM are also unknown.

Inclusion Criteria

• 14 (7 female/ 7 male) Type 2 diabetic patients age 18-60 yrs
• 14 (7 female/ 7 male) Non-diabetic controls age and weight matched
• Body mass index >20 kg/m2
• Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities
• Female volunteers of childbearing potential: negative HCG pregnancy test
• Volunteers over 40 years old: normal baseline cardiac stress test
• For those with type 2 diabetes: HBA1C >5.5%
• For those with type 2 diabetes: diabetes < 20 years
• For those with type 2 diabetes: C-peptide >0.2 nmol (1.1-4.4 ng/ml). If c-peptide is abnormal or there is a clinical suspicion of type 1 diabetes, MODY, or LADA, Anti-Islet cell (negative) and Glutamic Acid Decarboxylase (GAD) antibody negative (0.0-1.5 U/ml) will be performed

Exclusion Criteria

• Uncontrolled hypertension
• History of cerebrovascular incidents
• Pregnancy
• Subjects unable to give voluntary informed consent
• Subjects with a recent medical illness
• Subjects on anticoagulant drugs, anemic, or with known bleeding diseases
• Tobacco Use

Physical Exam Exclusion Criteria

• Blood Pressure greater than 150/95
• Clinically significant Cardiac Abnormalities (e.g. Heart Failure, Arrhythmias, ischemic tachycardia, S-T segment deviations, ect.) from history or from cardiac stress testing
• Pneumonia
• Hepatic Failure/Jaundice
• Renal Failure
• Acute Cerebrovascular/ Neurological deficit
• Fever greater than 38.0 C

Screening blood tests exclusions according to protocol