Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid
Condition: Diabetes Mellitus, Type 2; Hyperuricemia
MeSH terms: Diabetes Mellitus, Type 2; Hyperuricemia
Intervention: Low-fructose diet, isocaloric; Allopurinol; Placebo; Low-fructose, hypocaloric
Intervention description: 6 month of consumption a low fructose diet; 6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group; 6 months of placebo treatment; 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
Intervention MeSH terms: Allopurinol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 34.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: arterial stiffness; endothelial dysfunction; type 2 diabetes; hyperuricemia

Summary:

      Three separate interventions will be undertaken with the primary outcome of improving pulse
      wave velocity. Initially, age and BMI-matched men and post-menopausal women, all with type 2
      diabetes, will be treated with allopurinol (20 men, 20 women) for 6 months, in order to
      reduce serum uric acid (SUA) concentrations relative to placebo (10 men, 10 women). In a
      second intervention, dietary fructose will be restricted for a period of 6 months in type 2
      diabetes (T2D) subjects who will maintain a stable weight (20 men, 20 women). In a third
      intervention, dietary fructose will be restricted for a period of 6 months in type 2 diabetes
      (T2D) subjects who will achieve a caloric deficit and weight reduction (20 men, 20 women). At
      the beginning and end of each of the studies, measures of arterial stiffness will be combined
      with assessments of endothelial function (flow-mediated dilation and insulin stimulated leg
      blood flow), measurements of systemic inflammation and oxidative stress.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women ages 40-75 years at randomization

          -  BMI between 25.1 and 50 kg/m2.

          -  Type 2 diabetes diagnosed > 3 months ago. Patients with T2D will be classified based
             on physician diagnosis.

        Exclusion Criteria:

          -  serum uric acid < 5.5 mg/dL (for medication/allopurinol and isocaloric low-fructose
             diet arm)

          -  habitual diet containing low amount of sugars < 5% of total energy intake

          -  recent CVD event (stroke, heart failure hospitalization, revascularization or acute
             coronary event in the last 12 months).

          -  abnormal thyroid tests or chronic liver disease

          -  stage IV renal disease (GFR <30)

          -  hyperparathyroidism

          -  use of azathioprine

          -  active cancer

          -  autoimmune diseases

          -  excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women)

          -  current tobacco use

          -  bodyweight change ≥10% within the last 6 months

          -  history of gout or uncontrolled hypertension

          -  A1C >10 % (only for medication/placebo arm)

          -  Pregnancy or lactation in women (or women not using contraceptives)