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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Sedentary, overweight and obese subjects diagnosed with T2D, ages 40-75 years old, will be
      recruited from the local community, via the University of Missouri's Endocrinology Clinic and
      the primary care clinics. During screening, and after consent, anthropometrics (waist
      circumference and body composition) will be obtained and fasting blood will be drawn for
      serum chemistries, A1c, complete blood count, liver and kidney function. Screening will also
      include completion of an oral glucose tolerance test with measurements of arterial stiffness
      and assessment of endothelial function. Following screening, eligible subjects will be
      assigned to one of the four groups (allopurinol, placebo, fructose restriction/isocaloric, or
      fructose restriction/hypocaloric). Allopurinol will be titrated to achieve a target dose of
      300 mg/day. Along with placebo, this arm of the study is double-blinded. A separate group of
      men and women will be assigned to the isocaloric fructose-restriction study in which dietary
      fructose is replaced by starch and body weight is held constant. Lastly, a separate group of
      men and women will be assigned to the hypocaloric fructose-restriction in which baseline
      caloric intake will be reduced by 500 Calories/day while baseline intakes of protein and fat
      will remain constant. The subjects in these groups will not be blinded to the dietary
      treatment but the staff making measurements will be. Subjects in the four groups will be
      matched for age and BMI.
    

Intervention name(s): Low-fructose diet, isocaloric; Allopurinol; Placebo; Low-fructose, hypocaloric
Intervention type(s): Other; Drug; Drug; Other
Intervention description(s): 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
Other intervention name(s): Zyloprim
Intervention MeSH terms: Allopurinol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: arterial stiffness; endothelial dysfunction; type 2 diabetes; hyperuricemia