Type 2 Diabetes
Conditions
Keywords
Type 2 Diabetes, Endothelial Function, Fibrinolytic Balance, Hypoglycemia
Brief summary
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.
Detailed description
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.
Interventions
all participants received (2) hyperinsulinemic glucose clamp studies separated by 8 weeks
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2 | baseline on day 2 and ~6 hours later at end of glucose clamp period | A measure of the baseline arterial dilation on day 2 is compared to the post intervention measure of dilation of the brachial artery on Day 2. |
Countries
United States
Participant flow
Recruitment details
Individuals were recruited to participate in a cross-over design coming in for a 2 day study with an 8 week wash out period and then returning for another 2 day study. Individuals were randomized in the order of completing the control group (day 1 euglycemia, day 2 hypoglycemia) or antecedent hypo group (day 1 hypoglycemia, day 2 hypoglycemia).
Pre-assignment details
All participants completed both studies (either the control study (day 1 euglycemia, day 2 hypoglycemia) or the antecedent hypoglycemia study (day 1 hypoglycemia, day 2 hypoglycemia) in a random order with each study separated by an 8 week wash out period.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 35 years STANDARD_DEVIATION 1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2
A measure of the baseline arterial dilation on day 2 is compared to the post intervention measure of dilation of the brachial artery on Day 2.
Time frame: baseline on day 2 and ~6 hours later at end of glucose clamp period
Population: Flow mediated dilation of the brachial artery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2 | 2 percentage of change | Standard Error 1 |
| Antecedent Hypoglycemia Group | Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2 | 7 percentage of change | Standard Error 1 |