Prediabetic State
Conditions
Keywords
Glucose, Glucose Tolerance Test, Insulin Resistance, Metabolic adverse effects, Hypertension, Beta-blocker, Atenolol, Diuretic, Hydrochlorothiazide, Blood pressure
Brief summary
The purpose of this study is to determine if, in a subset of patients treated with a beta-blocker and diuretic, prediabetes is detectable to a greater extent through a 2-hour oral glucose tolerance test (OGTT) compared to fasting glucose measurement.
Detailed description
Beta-blockers and diuretics have a well-established role in treating hypertension and are frequently used first-line. However, it is increasingly evident that these medications have harmful metabolic effects. The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR - NCT00246519) study was a greater than 700 participant, randomized, parallel assignment trial, aimed at determining the genetic factors that influence response to both a beta-blocker (atenolol) and a diuretic (hydrochlorothiazide \[HCTZ\]). The PEAR trial design includes evaluation at baseline, after monotherapy with either medication, and after combination therapy with both medications. This pilot, PEAR sub-study aims to characterize the ability of two diagnostics tests (fasting glucose versus glucose 2-hours after an OGTT) to detect prediabetes development prior to blood pressure medication use, after monotherapy (with atenolol or HCTZ) and after combination therapy (with atenolol and HCTZ).
Interventions
OTHEROral glucose tolerance test
For assessment of dysglycemia, 75 grams of glucose solution by mouth at 3 PEAR study visits for all enrolled participants: baseline, single drug therapy assessment, and dual drug therapy assessment.
Sponsors
University of Florida
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* participation in PEAR: * an average seated home DBP \> 85 mmHg and home SBP \< 180 mmHg. * subjects must also have an average seated (\> 5 minutes) clinic DBP between 90 mmHg and 110 mmHg and SBP \< 180 mmHg.
Exclusion criteria
* secondary forms of HTN, * patients currently treated with three or more antihypertensive drugs, isolated systolic HTN, * other diseases requiring treatment with BP lowering medications, * heart rate \< 55 beats/min, * known cardiovascular disease (including history of angina pectoris, heart failure, presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or cerebrovascular disease, including stroke and TIA), * diabetes mellitus (Type 1 or 2), * renal insufficiency (serum creatinine \> 1.5 in men or 1.4 in women), * primary renal disease, * pregnancy or lactation, * liver enzymes \> 2.5 upper limits of normal, * current treatment with NSAIDS, * COX2-inhibitors, * oral contraceptives or estrogen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Baseline, 9 weeks, and 18 weeks after initiation of PEAR intervention(s) | A single cohort of patients was followed through participation in the parent study, PEAR, and had both fasting and 2-hour OGTT labs evaluated at three time points. At each of these time points the two methods for evaluating prediabetes were compared. Consistent with the definition for prediabetes recommended by the American Diabetes Association, a fasting glucose above 99mg/dL or 2-hour oral glucose tolerance test glucose above 139mg/dL was considered prediabetic for this study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PEAR Sub-study Participants All participants eligible for the PEAR study in Gainesville, FL, starting May 2009, were allowed to participate in the PEAR sub-study | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | PEAR Sub-study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age, Continuous | 46.7 years STANDARD_DEVIATION 11.1 |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 26 |
| serious Total, serious adverse events | 0 / 26 |
Outcome results
Primary
Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment
A single cohort of patients was followed through participation in the parent study, PEAR, and had both fasting and 2-hour OGTT labs evaluated at three time points. At each of these time points the two methods for evaluating prediabetes were compared. Consistent with the definition for prediabetes recommended by the American Diabetes Association, a fasting glucose above 99mg/dL or 2-hour oral glucose tolerance test glucose above 139mg/dL was considered prediabetic for this study.
Time frame: Baseline, 9 weeks, and 18 weeks after initiation of PEAR intervention(s)
Population: Only including participants with data at each time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-hour Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Prediabetic at baseline | 6 participants |
| 2-hour Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Normal glucose at baseline | 20 participants |
| 2-hour Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Prediabetic at 9 weeks | 7 participants |
| 2-hour Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Normal glucose at 9 weeks | 19 participants |
| 2-hour Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Prediabetic at 18 weeks | 7 participants |
| 2-hour Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Normal glucose at18 weeks | 15 participants |
| Fasting Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Prediabetic at 18 weeks | 9 participants |
| Fasting Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Prediabetic at baseline | 8 participants |
| Fasting Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Normal glucose at 9 weeks | 17 participants |
| Fasting Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Normal glucose at baseline | 18 participants |
| Fasting Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Normal glucose at18 weeks | 13 participants |
| Fasting Glucose | Number of Participants Diagnosed With Prediabetes or Normal Glucose, by 2 Measurements (Fasting Glucose Measurement and Glucose Measurement After a 2-hour Oral Glucose Tolerance Test [OGTT]), at Three Timepoints During Antihypertensive Treatment | Prediabetic at 9 weeks | 9 participants |
Comparison: p\<0.05 was considered significant at baseline; the null hypothesis was that there was no difference between prediabetes diagnosis (by 2-hour glucose or fasting glucose), the alternative hypothesis was that there was a significant difference between prediabetes diagnosis (by 2-hour glucose or fasting glucose)p-value: 0.41McNemar
Comparison: p\<0.05 was considered significant at 9 week assessment; the null hypothesis was that there was no difference between prediabetes diagnosis (by 2-hour glucose or fasting glucose), the alternative hypothesis was that there was a significant difference between prediabetes diagnosis (by 2-hour glucose or fasting glucose)p-value: 0.59McNemar
Comparison: p\<0.05 was considered significant at 18 week assessment; the null hypothesis was that there was no difference between prediabetes diagnosis (by 2-hour glucose or fasting glucose), the alternative hypothesis was that there was a significant difference between prediabetes diagnosis (by 2-hour glucose or fasting glucose)p-value: 0.41McNemar