The Effects of Potassium on Glucose Metabolism in African Americans
Condition: Borderline Hypokalemia
MeSH terms: Hypokalemia; Potassium Deficiency
Intervention: K+ supplement; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 61.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: borderline hypokalemia; glucose tolerance; insulin secretion; insulin sensitivity; fasting glucose; African American

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.
    

Eligibility criteria:

        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.