Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Carotid Femoral Pulse Wave Velocity (cfPWV)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ages 40-75 years at randomization
- •BMI between 25.1 and 50 kg/m
- •Type 2 diabetes diagnosed > 3 months ago. Patients with T2D will be classified based on physician diagnosis.
排除标准
- •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)
研究组 & 干预措施
Low-fructose diet, isocaloric
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose while maintaining baseline body weight.
干预措施: Low-fructose diet, isocaloric (Other)
Allopurinol
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
干预措施: Allopurinol (Drug)
Placebo
Subjects assigned to this arm will receive placebo
干预措施: Placebo (Drug)
Low-fructose diet, hypocaloric
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.
干预措施: Low-fructose, hypocaloric (Other)
结局指标
主要结局
Carotid Femoral Pulse Wave Velocity (cfPWV)
时间窗: This will be assessed at baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.
It is the gold standard non-invasive index of arterial stiffness. Transit time between carotid and femoral pressure waves is calculated using the foot-to-foot method. cfPWV is calculated as distance traveled by the pulse wave (i.e., femoral location-sternal notch minus sternal notch-carotid location) divided by pulse transit time. All the measurements will be done by the same blinded technician
次要结局
- Brachial Artery Flow Mediated Dilation (FMD)(Baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.)
- Insulin-stimulated Leg Blood Flow(The goal is to assess insulin stimulated responses in blood flow after 6 mo of intervention.)
研究者
Camila Manrique, MD
Associate Professor of Medicine
University of Missouri-Columbia