The Metabolic Effects of Different Weight Loss Diets
The Metabolic Effects of Different Weight Loss Diets
Current estimates suggest that 65% of American adults are overweight or obese. Excess body
 weight has been associated with an increased risk of a number of metabolic abnormalities,
 including high blood sugar, high blood pressure, high triglyceride levels, and low HDL
 ("good") cholesterol levels. Insulin resistance (when the body becomes less sensitive to the
 blood sugar-lowering hormone insulin, and more of the hormone is needed to keep blood sugar
 levels under control) also frequently occurs as a result of excess body weight. These
 abnormalities can all increase the risk of heart disease and other serious medical problems.
 Individuals who are overweight often have a number of these abnormalities at the same time, a
 situation which is often called "the metabolic syndrome." Dietary changes, physical activity,
 and weight loss can lead to improvements in each of the metabolic abnormalities described
 above. However, the best type of diet for people with the metabolic syndrome is not known.
 This study has been designed to test the effects of several promising dietary patterns, with
 and without weight loss, in overweight adults with the metabolic syndrome. Most individuals
 who have the metabolic syndrome do not know they have the condition, so we will be screening
 many healthy overweight volunteers to see if they may be eligible.
BACKGROUND:

 Several dietary approaches, including the Dietary Approaches to Stop Hypertension study diet
 (the DASH diet) and the low glycemic index diet (low GI diet), may be helpful for overweight
 individuals who have the metabolic syndrome. The DASH diet is rich in fruits, vegetables,
 whole grains, and low-fat dairy products. It also contains moderate amounts of nuts, beans,
 fish, and poultry. Consumption of red meat, sweets, and sugary beverages is limited. As a
 result, the DASH diet contains more potassium, magnesium, calcium, and fiber and less total
 fat, saturated fat, cholesterol, simple sugars, and sodium than the average American diet.
 The DASH diet has been shown to lower blood pressure and LDL cholesterol ("bad" cholesterol).
 It has also been shown to be an effective diet for weight loss. It may also reduce
 inflammation and insulin resistance, two important features of the metabolic syndrome.

 Low GI diets are typically lower in carbohydrate content and higher in protein content than
 the average American diet. Many popular diet books promote the use of low glycemic index
 diets. In this study, the low GI diet will contain plenty of fruits and vegetables and
 moderate amounts of nuts, beans, lean meats, fish, and reduced-fat dairy products. Refined
 grains, potatoes, and sweets will be avoided. The low GI diet can help improve levels of
 blood sugar and insulin in the blood after meals. It may also help control hunger after
 meals. Some researchers believe it may promote more weight loss than other diets, especially
 in people with the metabolic syndrome. The low GI diet may also reduce cholesterol and
 triglyceride levels.

 Although both the DASH diet and the low GI diet appear to have beneficial effects, it is not
 clear whether one diet is better than the other for people with the metabolic syndrome. It is
 also not clear whether these diets would be better for weight loss than a reduced-calorie
 average American diet. This weight loss study has been designed to test the metabolic effects
 of the DASH diet and the low GI diet, as compared to the average American diet.

 STUDY OVERVIEW:

 Up to 18 research volunteers will be studied at Rockefeller University Hospital during a
 multi-phase study of almost 15 weeks duration. This study includes a 2-week run-in period at
 home, a 19-day inpatient period during which weight will be kept stable, an 8-week outpatient
 weight loss period, and a 2-week inpatient period of weight stability at a lower body weight.
 All food will be provided for about 13 weeks (during the inpatient periods and the 8-week
 outpatient weight loss period). Volunteers will first undergo testing (described below) at
 baseline, on an average American diet. They will then be randomized to one of three diets
 (the DASH diet, the low GI diet, or the average American diet). Weight will initially be kept
 stable for two weeks on the study diet. At the end of the first inpatient period, volunteers
 will undergo repeat testing to assess the metabolic effects of the diets, in the absence of
 weight loss. Volunteers will then be discharged to home for 8 weeks, during which they will
 receive a 50% reduced-calorie study diet. Volunteers will return to Rockefeller University
 Hospital twice a week during the outpatient phase for weight-management skills training and
 follow-up with study staff. It is expected that volunteers will lose between 5 and 9% of
 their starting weights during this time. At the end of the weight loss phase, volunteers will
 be readmitted to the research hospital for a final 2-week stay. Body weight will be
 maintained at the new, lower weight, and volunteers will undergo repeat testing on the study
 diet. At the conclusion of testing, volunteers will be discharged from the hospital and the
 study will conclude.

 TESTING:

 During this study, a number of tests and procedures will be performed at various times. These
 will include:

 -  Questionnaires about physical activity, eating habits, attitudes about food,
 quality-of-life, and hunger

 -  A 3-day record of food intake at baseline

 -  Use of a pedometer (step-counter) to assess usual physical activity

 -  Blood tests (including blood sugar, insulin levels, cholesterol levels, fat hormones,
 and inflammatory markers)

 -  24-hour ambulatory blood pressure monitoring

 -  Measurement of energy expenditure (the rate at which a body burns calories)

 -  Noninvasive assessment of body composition before and after weight loss

 -  Insulin clamp procedures (during which insulin and sugar are infused through a vein to
 help determine how sensitive a person's body is to insulin)
Inclusion Criteria:

 -  Nonsmoking men and premenopausal women, ages 18-45

 -  Body mass index ≥ 27 kg/m2

 -  Body weight < 200 kg

 -  Evidence of insulin resistance, as suggested by any one of the following:

 -  Fasting glucose ≥ 100 mg/dL

 -  Impaired glucose tolerance, with a glucose concentration of ≥ 140 mg/dL 2 hours after
 a 75-gram oral glucose challenge

 -  A fasting insulin concentration ≥ 9 mIU/L

 -  At least two of the following:

 -  Waist circumference > 35" in women or > 40" in men

 -  Prehypertension or hypertension, with BP > 120/80 mmHg but < 145/90 mmHg on 2
 antihypertensive agents or less

 -  TG > 150 but < 500 mg/dL

 -  HDL < 40 mg/dL in men or < 50 mg/dL in women

 -  Willingness to consume only study food and drink for the duration of the study and to
 be randomized to one of the three diets

 -  Willingness to maintain consistent intake of coffee and/or tea during the inpatient
 periods

 -  Willingness to avoid the use of all over-the-counter or prescription vitamins, dietary
 supplements, and herbal products during the study, with the exception of the
 multivitamin supplement (Flintstones® Plus Iron.)

 -  Willingness to continue current antihypertensive medications at the same dose and
 schedule throughout the study, unless a change is advised.

 -  Willingness to avoid the use of non-steroidal anti-inflammatory drugs including
 low-dose daily aspirin, for at least ten days prior to the first admission and during
 each admission.

 -  Willingness to avoid the use of acetaminophen (Tylenol) and furosemide (Lasix) for at
 least 48 hours prior to and during the 24-hour urine collection.

 -  Willingness to avoid the use of sulfonamide antibiotics for at least 1 week prior to
 and during the 24-hour urine collection.

 Exclusion Criteria:

 -  Current tobacco smoking

 -  History of a bleeding disorder

 -  Findings suggestive of cardiovascular disease.

 -  Blood pressure ≥ 145/90 mmHg after 10 minutes of rest on two or more screening visits,
 or treatment with three or more antihypertensive agents at any blood pressure.

 -  Fasting glucose ≥ 165 mg/dL, glycosylated hemoglobin > 8%, or any treatment with oral
 hypoglycemic agents, insulin sensitizing agents , insulin, incretin mimetics, amylin
 analogues, or endocannabinoid receptor antagonists.

 -  History of chronic glucocorticoid use, oral glucocorticoid use for more than 5 days in
 the previous year, or anticipated treatment with oral or intravenous glucocorticoids
 during the study period.

 -  Current treatment with weight loss medications.

 -  History of bariatric surgery

 -  Current treatment with any cholesterol-lowering medications.

 -  Hyperthyroidism or untreated hypothyroidism.

 -  Pregnancy, desired pregnancy, or lactation within the study period.

 -  Peri- or postmenopausal status.

 -  Obstructive sleep apnea.

 -  Active gallstone disease

 -  Known history of chronic hepatitis, or liver enzymes more than 2.5 times the upper
 limit of normal

 -  Known infection with HIV or confirmed positive test for HIV antibody

 -  Inflammatory bowel disease, active cancer, or any other medical condition that may
 cause significant acute weight loss or gain

 -  Sustained weight loss > 5% of body weight in the previous two months, or sustained
 weight loss > 10% of body weight in the previous six months

 -  History of kidney stones

 -  Renal disease, as evidenced by a serum creatinine above the normal limit on more than
 one screening visit

 -  Serum calcium, potassium, or magnesium above the normal limit, confirmed on two
 screening tests

 -  Seizure disorder

 -  History of any inpatient psychiatric admission within the past two years

 -  History of schizophrenia, psychosis, or bipolar disorder

 -  History of anorexia nervosa or bulimia nervosa or a history of medical or
 psychological treatment for an eating disorder

 -  Severe binge eating disorder

 -  Active moderate to severe depression.

 -  History of alcohol or drug abuse within the previous two years

 -  History, physical, or laboratory findings suggestive of any other medical or
 psychological condition that would, in the opinion of the principal investigator, make
 the candidate ineligible for the study