Borderline Hypokalemia
Conditions
Keywords
borderline hypokalemia, glucose tolerance, insulin secretion, insulin sensitivity, fasting glucose, African American
Brief summary
African Americans suffer a disproportionately high risk of diabetes compared to other Americans. Reasons for race disparities in diabetes incidence are not completely understood. Although a difference in prevalence of obesity does explain a significant portion of the racial disparity in diabetes risk, it does not explain all of this disparity. Strategies to control the diabetes epidemic and reduce its racial disparity often overlook preventive measures. Currently, the most powerful known strategy for preventing diabetes is weight loss in the overweight/obese. However, because weight loss is often difficult to achieve and maintain, other opportunities to prevent diabetes should be identified, particularly in African Americans. Among potential novel opportunities is correction of low or low-normal potassium levels (hypokalemia). In secondary analyses, we have found low-normal potassium (K) to be a novel risk factor for diabetes; and we have found that this association between low-K and diabetes risk may be stronger in African Americans compared to whites. Therefore, a previously unrecognized alternative or adjunct strategy for preventing diabetes, particularly in African Americans, may involve correction of low or low-normal K levels (hypokalemia). Large-scale, adequately-powered, randomized controlled trials are needed to establish the effectiveness of this approach. However, prior to those trials, the pathophysiology of the association between low K and poor glucose metabolism must be understood. This pilot clinical trial will begin to determine the effect of K supplementation on measures of glucose metabolism in African Americans. In this pilot clinical trial, 30 African Americans with prediabetes and a low-normal serum K \[\<4.0 milliequivalent/Liter (Eq/L)\] will be randomized to K-supplements, 20mEq (2-10mEq tablets) twice daily or a matching placebo capsules twice daily. Prior to randomization, baseline measures will be taken including measures of glucose metabolism with a 3-hour oral glucose tolerance test (OGTT), baseline chemistries and a baseline 24-hour urinary potassium measurement. Patients will take the intervention daily and will undergo repeat testing of all of these measures at the end of a 3 month period. The primary endpoint will be change in glucose tolerance, as measured by change in glucose area-under-the-curve (AUC) of a 3-hour oral glucose tolerance test (OGTT). Secondary endpoints will include changes in fasting, 1-hour, and 2-hour post-challenge glucose levels, as well as measurements of insulin secretion and insulin sensitivity as measures by the oral glucose minimal model method.(1) The baseline data from this trial will allow us to quantify abnormalities in glucose metabolism in African Americans with prediabetes/early diabetes and low-normal serum K. The post-intervention data will provide estimates of the impact of K-supplements compared to no supplements on these abnormalities. Data derived from the pilot study will be used in the design of a larger scale, adequately powered clinical trial. This trial will also help to assess the feasibility of recruiting this target population. With this pilot trial, we will begin to determine whether or not K-supplements, an inexpensive, well-tolerated, and simple intervention, could help to reduce diabetes risk among African Americans.
Interventions
DRUGPlacebo
DRUGK+ supplement
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for inclusion in the study the following enrollment criteria must be met: 1. Participants must be 30 years of age or older. 2. They must have a diagnosis of prediabetes defined as a hemoglobin A1c between 5.7-6.5% measured at the initial screening visit. 3. They must have a serum K+ of 3.3-4.0 mEq/L on 2 occasions, within a 18 month period, including at initial screening visit. If subject is just outside range for inclusion, PI may offer the subject the option to repeat their screening serum K+ measurement. 4. The participant must be willing and capable of providing written informed consent. 5. The participant must be available for follow-up and must at minimum have telephone access. 6. Participants must be able to read/understand English.
Exclusion criteria
* Participants must not have any of the following: 1. Participants must not have evidence of chronic kidney disease with an estimated Glomerular Filtration Rate (eGFR) \< 60ml/min. All patients will be screened for eGFR at the enrollment visit. 2. Participants must not have evidence of diabetes mellitus requiring treatment with medications prior to screening visit. The cannot have a random or post-challenge glucose ≥ 200mg/dl (from prior labs), A1c level ≥ 6.5% (from prior labs), prior physician diagnosis, or use of anti-diabetic medications. If participants have glucose levels in the diabetic range at screening visit, they will be eligible to continue in study as long as glucose levels are not \> 200 mg/dl. 3. Participants must not have a history of endoscopy-verified peptic ulcer disease with past history of either gastric or duodenal ulcer. 4. Participants must not have evidence of cardiac arrhythmias, unstable angina or cardiac event within 6 months, congestive heart failure, or other conditions that might impact follow-up, based on the discretion of the principal investigator. 5. Participants must not be pregnant or intend to get pregnant during the study period. The study intervention is safe for pregnant women, so serum pregnancy screening is not indicated; however, pregnant women are excluded because pregnancy affects glucose homeostasis, which will bias primary outcome measurement and damage scientific validity of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glucose Tolerance as Measured by Area-under-the-curve | Baseline to 3 months | Change in glucose tolerance, as measured by change in glucose area-under-the-curve (Area Under the Curve (AUC) - measured via the trapezoidal method) of 2 hours from the 3-hour Oral Glucose Tolerance Test (OGTT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL | Baseline to 3 months | Changes in fasting, 1-hour, and 2-hour post-challenge glucose levels in mg/dL |
| Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC) | Baseline to 3 months | Changes in Insulin Secretion as measured by 2-hour insulin area-under-the-curve (AUC - measured via the trapezoidal method) of 2 hours from the 3-hour OGTT. |
| Changes in Insulin Sensitivity | Baseline to 3 months | Matsuda Insulin Sensitivity Index was calculated as: 10,000 / square root of \[fasting glucose x fasting insulin x mean glucose x mean insulin during Oral Glucose Tolerance Test\]). |
Countries
United States
Participant flow
Pre-assignment details
61 participants (17%) expressed interested in the study and signed informed consent. Of these, 29 participants were deemed eligible based on the results of the screening labs
Participants by arm
| Arm | Count |
|---|---|
| K+ Supplementation K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months
K+ supplement | 15 |
| Placebo Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months
Subjects will be instructed to take the pills
Placebo | 12 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | K+ Supplementation | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 11 | 52.7 years STANDARD_DEVIATION 8.9 | 55.0 years STANDARD_DEVIATION 10.2 |
| BMI | 34.3 kg/m2 STANDARD_DEVIATION 5.4 | 35.1 kg/m2 STANDARD_DEVIATION 5.2 | 34.8 kg/m2 STANDARD_DEVIATION 5.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 12 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 15 participants | 12 participants | 27 participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 0 / 15 | 1 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 |
Outcome results
Primary
Change in Glucose Tolerance as Measured by Area-under-the-curve
Change in glucose tolerance, as measured by change in glucose area-under-the-curve (Area Under the Curve (AUC) - measured via the trapezoidal method) of 2 hours from the 3-hour Oral Glucose Tolerance Test (OGTT).
Time frame: Baseline to 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K+ Supplementation | Change in Glucose Tolerance as Measured by Area-under-the-curve | 328 AUC - mg*min/dL | Standard Deviation 1779 |
| Placebo | Change in Glucose Tolerance as Measured by Area-under-the-curve | 1000 AUC - mg*min/dL | Standard Deviation 2378 |
p-value: 0.5582ANCOVA
Secondary
Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL
Changes in fasting, 1-hour, and 2-hour post-challenge glucose levels in mg/dL
Time frame: Baseline to 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| K+ Supplementation | Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL | Change in Fasting Glucose | -1.0667 mg/dL | Standard Deviation 8.3961 |
| K+ Supplementation | Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL | Change in 1-Hour Glucose | 0.80 mg/dL | Standard Deviation 31.36 |
| K+ Supplementation | Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL | Change in 2-Hour Glucose | 3.60 mg/dL | Standard Deviation 25.82 |
| Placebo | Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL | Change in Fasting Glucose | 6.0833 mg/dL | Standard Deviation 7.6093 |
| Placebo | Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL | Change in 1-Hour Glucose | 14.17 mg/dL | Standard Deviation 37.07 |
| Placebo | Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL | Change in 2-Hour Glucose | 0.75 mg/dL | Standard Deviation 24.53 |
p-value: 0.0963ANCOVA
p-value: 0.6671ANCOVA
p-value: 0.7913ANCOVA
Secondary
Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC)
Changes in Insulin Secretion as measured by 2-hour insulin area-under-the-curve (AUC - measured via the trapezoidal method) of 2 hours from the 3-hour OGTT.
Time frame: Baseline to 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| K+ Supplementation | Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC) | 71,444 AUC - pg*min/mL |
| Placebo | Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC) | 149,327 AUC - pg*min/mL |
p-value: 0.5294ANCOVA
Secondary
Changes in Insulin Sensitivity
Matsuda Insulin Sensitivity Index was calculated as: 10,000 / square root of \[fasting glucose x fasting insulin x mean glucose x mean insulin during Oral Glucose Tolerance Test\]).
Time frame: Baseline to 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K+ Supplementation | Changes in Insulin Sensitivity | -0.03 AUC - unitless, | Standard Deviation 1.49 |
| Placebo | Changes in Insulin Sensitivity | -0.87 AUC - unitless, | Standard Deviation 1.13 |
p-value: 0.1604ANCOVA