Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adverse Metabolic Effects of Dietary Sugar: Ad Libitum vs Energy-balanced Diets
Brief Summary: It is not known whether consumption of excessive amounts of sugar can increase risk factors for cardiovascular disease or diabetes in the absence of increased food (caloric) intake and weight gain, nor whether the negative effects of sugar consumption are made worse when accompanied by weight gain. This study will investigate the effects of excess sugar when consumed with an energy-balanced diet that prevents weight gain, and the effects of excess sugar when consumed with a diet that can cause weight gain. The results will determine whether excess sugar consumption and excess caloric intake that lead to weight gain have independent and additive effects on risk factors for cardiovascular disease or diabetes, and will have the potential to influence dietary guidelines and public health policy.


Options:
A: A) Inclusion Criteria:

Eligible participants will be:

1. men, over 50
2. postmenopausal women, over 60 or
3. postmenopausal women under 60 with a family history of hypercholesterolemia and 1 CVD risk factor.

Participants will have the following characteristics:

* BMI 25-40 kg/m2 with body weight that has remained constant (within ±3%) over the last 3 months preceding the onset of the study
* Plus at least 1 of the following 3 criteria:

  1. have type 2 diabetes with one of the following:

     * raised LDL-C(in accordance with the 2012 Canadian Cardiovascular Society Guidelines)
     * raised BP (\> 130/80mmHg), or
     * active smoking;
  2. be non-diabetic subjects post MI or post percutaneous coronary intervention (angioplasty) on statin therapy; and
  3. have a modified Framingham risk score \>20% (CCS 2012) and are unable (intolerant) or unwilling to take statin drugs.

B) Exclusion Criteria:

Individuals with the following conditions will be excluded:

* cardiovascular disease that precludes exercise e.g.

  * recent stroke or
  * myocardial infarction, or
* cardiac condition that compromises normal function

  * mitral valve disease,
  * heart failure--grades 2-4 (New York Heart Association classification),
  * severe angina or
  * other conditions preventing exercise,
* secondary causes of hypercholesterolemia

  * hypothyroidism, (unless treated and on a stable dose of L-thyroxine)
  * renal or liver disease
* uncontrolled blood pressure
* major disability
* disorder requiring continuous medical attention and treatment:

  * chronic heart failure,
  * liver disease,
  * renal failure or
  * cancer (except non-melanoma skin cancer--basal cell, squamous cell),
* chronic infections (bacterial or viral)
* chronic inflammatory diseases (e.g. lupus, ulcerative colitis)
* other autoimmune diseases
* major surgery \<6 months prior to randomization
* alcohol consumption \>2 drinks/d.
B: Inclusion Criteria:

* subject is male or female, 18-74 yrs of age, inclusive
* subject reports habitual consumption of ≥2 servings/d of high-sugar beverages (e.g., non-diet soda, fruit juice cocktails)
* subject has waist circumference ≥33.0 inches for women and ≥36.0 inches for men
* subject is at risk for development of type 2 diabetes mellitus (T2DM), based on 1 or more of the following: fasting glucose 100-125 mg/dL; glycosylated hemoglobin 5.7-6.4%, or ≥20% risk of developing diabetes in the next 7.5 yrs based on the San Antonio Heart Study prediction equation
* subject has a score of 7-10 on the Vein Access Scale at screening
* subject is normally active and judged to be in good health on the basis of medical history, physical examination and routine lab tests
* if female, subject is willing to schedule treatment visits during the follicular phase of the menstrual cycle, defined as days 1-14, where day 1 is 1st day of menses
* subject has a menstrual cycle duration ranging in length form 24-36 d (if premenopausal)
* subject is willing to maintain a stable body weight and follow his/her habitual diet and exercise pattern, except for inclusion of study product, throughout the trial
* subject is willing to maintain his or her habitual intake of coffee, tea, and alcoholic beverages throughout the trial
* subject agrees to limit intake of non-study related dairy products to ≤1 serving per day during each treatment period
* subject is ambulatory and willing to refrain from vigorous physical activity and consumption of alcoholic beverages 24 h prior to each test day
* subject has no plans to change smoking habits during the study period
* subject is willing to abstain from tobacco use 1 h prior to and during visits on LMTT test days
* subject has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the Investigator on the basis of medical history and routine lab test results

Exclusion Criteria:

* subject has abnormal lab test results of clinical importance, including, but not limited to, TG ≥400 mg/dL, fasting creatinine ≥1.5 mg/dL, alanine aminotransferase or aspartate aminotransferase ≥1.5 times the upper limit of normal at screening
* subject has a body mass index ≥45.0 kg/m2
* subject has fasting blood glucose ≥126 mg/dL at screening or known diabetes mellitus (type 1 or T2DM)
* subject has a habitual intake of ≥4 servings/d of dairy food and beverages
* subject has known allergy or sensitivity to study product or any ingredients of study product. Subjects with lactose intolerance will be allowed to use products such as Lactaid dietary supplements
* subject has a history of coronary heart disease, congestive heart failure, or serious ventricular dysrhythmias (ventricular tachycardia or fibrillation)
* subject has a change in body weight of \>4.5 kg within 4 weeks of screening
* subject uses medications known to influence carbohydrate metabolism
* subject has recent use of antibiotics
* subject has an active infection
* subject has unstable use of anti-hypertensive medications, thyroid hormone replacement, or lipid-altering drugs within 4 weeks of screening
* subject has unstable use of lipid-altering foods or dietary supplements within 4 weeks of screening
* subject uses niacin at doses \>200 mg/d within 4 weeks of screening
* subject has history of extreme dietary habits, e.g., Atkins, high protein
* subject has a history or presence of clinically important endocrine, cardiac, renal, hepatic, pulmonary, biliary, pancreatic, gastrointestinal, or neurologic disorders that could interfere with interpretation of study results
* subject has history of dysphagia, swallowing disorders, or intestinal motility disorders
* subject has history of cancer
* subject has uncontrolled hypertension at screening (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg)
C: Inclusion Criteria:

* BMI 22-28 kg/m2
* Self-reported stable body weight during the prior six months

Exclusion criteria:

* Fasting glucose \>105 mg/dl
* Evidence of liver disorder \[AST (Aspartate Aminotransferase) or ALT (Alanine Aminotransferase)\] \>200% upper limit of normal range)
* Evidence of kidney disorder (\>2.0mg/dl creatinine)
* Evidence of thyroid disorder (out of normal range)
* Systolic blood pressure consistently over 140mm Hg (mercury) or diastolic blood pressure over 90mmHg
* Triglycerides \> 200mg/dl
* LDL-C \> 130mg/dl in combination with Chol:HDL \> 4
* Hemoglobin \< 8.5 g/dL
* Pregnant or lactating women
* Any other condition that, in the opinion of the investigators, would put the subject at risk
* Current, prior (within 12 months), or anticipated use of any hypolipidemic or anti-diabetic agents.
* Use of thyroid, anti-hypertensive, anti-depressant, weight loss medications or any other medication which, in the opinion of the investigator, may confound study results
* Use of tobacco
* Strenuous exerciser (\>3.5 hours/week at a level more vigorous than walking)
* Surgery for weight loss
* Diet exclusions: Food allergies, special dietary restrictions, food allergies, routine consumption of less than 3 meals/day, routine ingestion of more than 2 sugar-sweetened beverages or 1 alcoholic beverage/day, unwillingness to consume any food on study menu
* Hydrogen concentration in breath sample following consumption of HFCS-beverage during screening \>50ppm
* Veins that are assessed by the CCRC (Clinical Research Center) R.N.s as being unsuitable for long-term infusions and multiple blood draws from a catheter.
* Pre-existing claustrophobia or metal implants that preclude MRI
D: Inclusion Criteria:

* Healthy, adult (age, 18-75 years) men and non-pregnant women;
* Overweight or obese (BMI \> 23 kg/m2 for Asian individuals and \> 25 kg/m2 other individuals);
* High waist circumference (\> 94 cm in men, \> 80 cm in women in Europid, Sub-Saharan African, Eastern Mediterranean, and Middle Eastern individuals; \> 90 cm in men and \> 80 cm in women for South Asian, Chinese, Japanese, and South and Central American individuals);
* Currently report drinking SSBs regularly (≥ 1 serving daily);
* Have a primary care physician;
* Nonsmoker;
* Free of any diseases or illnesses;
* Not regularly taking any medications that have a clinically relevant effect on the primary outcomes, as deemed inappropriate by investigators

Exclusion Criteria:

* Age \< 18 or \> 75 years;
* BMI \< 23 kg/m2 for Asian individuals and \< 25 kg/m2 other individuals;
* Waist circumference \< 94cm in men, \< 80cm in women in Europid, Sub-Saharan African, Eastern Mediterranean, and Middle Eastern individuals; \< 90cm in men and \< 80 cm in women for South Asian, Chinese, Japanese, and South and Central American individuals;
* Not regularly drinking SSBs (≥1 serving per day);
* Pregnant or breast feeding females, or women planning on becoming pregnant throughout study duration;
* Regular medication use that have a clinically relevant effect on the primary outcomes, as deemed inappropriate by investigators
* Antibiotic use in the last 3 months;
* Complementary or alternative medicine (CAM) use as deemed inappropriate by investigators;
* Self-reported diabetes;
* Self-reported uncontrolled hypertension (or systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg \[26\]);
* Self-reported polycystic ovarian syndrome;
* Self-reported cardiovascular disease;
* Self-reported gastrointestinal disease;
* Previous bariatric surgery;
* Self-reported liver disease;
* Self-reported uncontrolled hyperthyroidism or hypothyroidism;
* Self-reported kidney disease;
* Self-reported chronic infection;
* Self-reported lung disease;
* Self-reported cancer/malignancy;
* Self-reported schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, and dissociative disorders;
* Major surgery in the last 6 months;
* Other major illness or health-related incidence within the last 6 months;
* Smoker;
* Regular recreational drug users;
* Heavy alcohol use (\> 3 drinks/day);
* Do not have a primary care physician;
* Participation in any trials within the last 6 months or for the duration of this study;
* Individuals planning on making dietary or physical activity changes throughout study duration;
* If participating in MRI portion of study: any condition or circumstance which would prevent the participant from having an MRI (e.g. having prostheses or metal implants, tattoos, or claustrophobia)

Answer: C