Drug Induced Hyperglycemia, Secondary Hyperlipidemia
Conditions
Brief summary
This is a research study of the long term effects on blood sugar and cholesterol of blood pressure lowering medications. People are invited to participate in this research study if they participated in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR 1, NCT00246519 or PEAR 2, NCT01203852) study and are still taking a thiazide diuretic. In PEAR, the effects on blood pressure, blood sugar, and cholesterol of the high blood pressure drugs hydrochlorothiazide and atenolol over an 18 week period were evaluated. This PEAR follow-up study will determine the effects of thiazide diuretics on blood sugar and cholesterol, but in the period since the PEAR trial. The study hypothesis is that long term exposure to thiazide diuretics results in larger increases in blood sugar and cholesterol levels than short term exposure.
Detailed description
One in three deaths in the United States is due to cardiovascular (CV) disease. One in three US adults has hypertension, a major underlying cause of CV disease. Type 2 diabetes (T2D) and dyslipidemia are major contributors of CV morbidity and mortality among hypertensive patients. Thiazide diuretics and beta blockers are first line agents in the treatment of hypertension, but these commonly prescribed antihypertensive classes can contribute to dysfunction of glucose and lipid metabolism. In randomized controlled trials, reductions in CV outcomes due to blood pressure reduction with thiazide diuretic and beta blocker treatment are accompanied by increases in T2D incidence and exacerbation of dyslipidemia. CV morbidity and mortality resulting from persistent antihypertensive-related T2D or dyslipidemia may eventually outweigh benefits from blood pressure reduction, encouraging use of alternate antihypertensive classes especially in high risk patients. An accumulating body of published literature supports that adverse metabolic effects are induced by thiazide diuretics and beta blockers. However, the vast majority of evidence for adverse metabolic effects of antihypertensive drugs utilizes secondary analyses of data from randomized blood pressure reduction trials. To date, no published study has compared short and long term adverse metabolic effects of antihypertensive therapy in the same patient population. The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study is a randomized, parallel assignment trial to determine genetic influences on blood pressure response to the thiazide diuretic hydrochlorothiazide and the beta blocker atenolol. The PEAR study duration (18 weeks) is not sufficient to assess long term effects (over six months) of these antihypertensive medications. The primary aim of this study is to determine the effects of long term thiazide and beta blocker therapy on glucose and lipid metabolism in the PEAR population, in which short term effects have been assessed. Secondary analyses of this follow-up study include investigating adverse metabolic effects of long term thiazide diuretic and beta blocker therapy on insulin sensitivity and the role of potassium and uric acid in the hyperglycemic effects of thiazide diuretics.
Interventions
DRUGOral Glucose Tolerance Test
Administration of 75 gram oral glucose load and three plasma glucose measurements (including baseline).
Sponsors
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* previously enrolled in PEAR study * completed last PEAR study visit greater than 6 months prior * receive thiazide diuretic continuously since PEAR enrollment
Exclusion criteria
* pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fasting Glucose (mg/dL) | Fasting glucose was obtained at time 0 min. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oral Glucose Tolerance Test (mg/dl h) | one oral glucose tolerance test was performed with 3 time points (0 hour, 1 hour, 2 hour) | Area under the curve for the OGTT was calculated for each patient using the 3 time points (0 hour, 1 hour and 2 hour). Average value for participants is provided. |
| Triglycerides (mg/dL) | Triglycerides was obtained at time 0 min. | — |
| Low Density Lipoprotein (mg/dL) | Low Density Lipoprotein was obtained at time 0 min. | — |
| High Density Lipoprotein (mg/dL) | High Density Lipoprotein was obtained at time 0 min. | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Follow-Up Arm All patients are recruited for inclusion in the Follow-Up Arm, which is the sole arm of the study. The Follow-Up Arm includes a one time study visit in which study interventions are performed.
Oral Glucose Tolerance Test: Administration of 75 gram oral glucose load and three plasma glucose measurements (including baseline). | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 4 |
Baseline characteristics
| Characteristic | Follow-Up Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants |
| Age, Continuous | 49 years STANDARD_DEVIATION 10 |
| Fasting Glucose | 91 mg/dL STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 44 |
| serious Total, serious adverse events | 0 / 44 |
Outcome results
Primary
Fasting Glucose (mg/dL)
Time frame: Fasting glucose was obtained at time 0 min.
Population: A total of 44 patients were included in the study, however 4 patients were treated with anti-diabetic medications and so were excluded from the analysis. Therefore there are a total of 40 patients that were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Follow-Up Arm | Fasting Glucose (mg/dL) | 94 mg/dL | Standard Deviation 13 |
Secondary
High Density Lipoprotein (mg/dL)
Time frame: High Density Lipoprotein was obtained at time 0 min.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Follow-Up Arm | High Density Lipoprotein (mg/dL) | 52 mg/dL | Standard Deviation 17 |
Secondary
Low Density Lipoprotein (mg/dL)
Time frame: Low Density Lipoprotein was obtained at time 0 min.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Follow-Up Arm | Low Density Lipoprotein (mg/dL) | 117 mg/dL | Standard Deviation 36 |
Secondary
Oral Glucose Tolerance Test (mg/dl h)
Area under the curve for the OGTT was calculated for each patient using the 3 time points (0 hour, 1 hour and 2 hour). Average value for participants is provided.
Time frame: one oral glucose tolerance test was performed with 3 time points (0 hour, 1 hour, 2 hour)
Population: Patients that underwent an OGTT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Follow-Up Arm | Oral Glucose Tolerance Test (mg/dl h) | 273 mg/dL*h | Standard Deviation 74 |
Secondary
Triglycerides (mg/dL)
Time frame: Triglycerides was obtained at time 0 min.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Follow-Up Arm | Triglycerides (mg/dL) | 157 mg/dl | Standard Deviation 89 |