Clinical trial NCT01661426: Weight Loss Diet Study: Low Carb vs Low Fat
Official title: Weight Loss Diet Study: Low Carbohydrate vs. Low Fat and Insulin Resistance Status
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Insulin Resistance
Keywords: Adults
Weight loss
Diet
Insulin Resistance
Fatty acid composition
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Hass Avocado Board
First posted: 2012-08-09
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study employed a 2 x 2 crossover design: LF vs. LC diets and more IR vs. more IS. Study participants were classified as more IR or more IS based on the median AUC for insulin concentrations measured from an oral glucose tolerance test (OGTT) prior to randomization. Participants above the median were considered more IR and those below the median were considered more IS. A random number generator was used to stratify the randomization to LF vs. LC by insulin resistance status and gender. Participants followed their assigned diet for 6 months and then switched to the opposite diet for another 6 months.
Primary purpose: PREVENTION

Brief summary: The traditional weight loss diet recommended by health professionals has been a low-fat, high-carbohydrate, calorie restricted diet. This recommendation has been challenged by a number of alternative dietary strategies, particularly low-carbohydrate diets. In several recent weight loss studies insulin resistant adults had more success with low- vs. high-carbohydrate diets, in contrast to insulin sensitive adults who had either more success or comparable success with the low-fat diets. The investigators enrolled 61 people with a wide range of insulin sensitivity/resistance. After determining their insulin resistance status, the investigators will split them in the middle and randomly assign them to one of four groups for six months: (1) Low-Carbohydrate/Insulin Resistant (LC/IR); (2) Low-Carbohydrate/Insulin Sensitive (LC/IS); (3) Low-Fat/Insulin Resistant (LF/IR); and (4) Low-Fat/Insulin Sensitive (LF/IS) (15 people/group). After 6 months the participants will switch diet for the following 6 months, i.e. those randomized to the Low-Carbohydrate diet will switch to the Low-Fat diet and vice-versa. The primary outcome of this study is to determine whether weight loss success can be increased if one follows the dietary approach appropriately matched to their insulin resistance status. Secondary outcomes include fasting insulin, glucose, lipids, and fatty acid composition.

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Detailed description: The investigators hope to learn whether matching the weight loss diet to one's insulin resistance status will increase weight loss the success. The relevance of these findings is highlighted by the fact that the national recommendations for weight loss are to follow a high-carbohydrate, low-fat diet. This would imply that about half the population has been given the wrong advice in regards to the most successful dietary pattern for weight loss.

Plasma fatty acid composition patterns have been shown to be associated with both insulin resistance and/or carbohydrate intake. As secondary analyses, the investigators will explore: (1) differences in plasma fatty acid composition between insulin sensitive and resistant participants at baseline; (2) the correlations between insulin markers and plasma fatty acid composition at baseline; (3) the interaction between insulin status and diet on 6-month changes in the plasma fatty acid composition; (4) plasma fatty acid composition changes in participants on low fat and low carbohydrate diets after 6 months; and (5) the correlations between changes in insulin markers, dietary components, and plasma fatty acid composition after 6 months.

Eligibility criteria: Inclusion Criteria:

* Age: \> or = 18 years of age
* Women: Pre-menopausal (self-report) and \<50 years of age
* Men: \<50 years of age
* Race/Ethnicity: All
* BMI (body mass index): 28-40 kg/m2 (need to lose \>10% body weight to achieve healthy BMI)
* Body weight stable for the last two months, and not actively on a weight loss plan
* No plans to move from the area over the next 14 months
* Available and able to participate in the evaluations and intervention for the study period
* Willing to accept random assignment
* To enhance study generalizability, people on medications not noted below as specific exclusions can participate if they have been stable on such medications for at least three months
* Ability and willingness to give written informed consent
* No known active psychiatric illness

Exclusion Criteria:

* Pregnant, lactating, within 6 months post-partum, or planning to become pregnant in the next 12 months; no menstruation for the previous 12 months
* Diabetes (type 1 and 2) or history of gestational diabetes or on hypoglycemic medications for any other indication
* Prevalent diseases: Malabsorption, renal or liver disease, active neoplasms, recent myocardial infarction, hypertension (except for those stable on hypertensive medications) (\<6 months) (patient self-report and, if available, review of labs from primary care provider)
* Smokers (because of effect on weight and lipids)
* History of serious arrhythmias, or cerebrovascular disease
* Uncontrolled hyper- or hypothyroidism (TSH not within normal limits)
* Medications: Lipid lowering, diabetes medications, and those known to affect weight/energy expenditure
* Excessive alcohol intake (self-reported, \>3 drinks/day)

Primary outcomes:
measure: Change in weight
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Change in Fasting Insulin
timeFrame: Baseline and 12 months
measure: Change in insulin AUC
timeFrame: Baseline and 12 months
measure: Change in Fasting Glucose
timeFrame: Baseline and 12 months
measure: Change in LDL-Cholesterol
timeFrame: Baseline and 12 months
measure: Change in HDL-Cholesterol
timeFrame: Baseline and 12 months
measure: Change in Triglycerides
timeFrame: Baseline and 12 months
measure: Change in systolic and diastolic blood pressure
timeFrame: Baseline and 12 months
measure: Plasma fatty acid composition at baseline
timeFrame: Baseline
measure: Correlations between insulin markers and plasma fatty acid composition at baseline.
timeFrame: Baseline
measure: Interaction between insulin status and diet on 6-month changes in the plasma fatty acid composition.
timeFrame: 6 months
measure: Comparison of plasma fatty acid composition changes in participants on low fat and low carbohydrate diets after 6 months.
timeFrame: Baseline and 6 months
measure: Correlations between changes in insulin markers, dietary components, and plasma fatty acid composition after 6 months.
timeFrame: 6 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Christopher D Gardner, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gardner CD, Offringa LC, Hartle JC, Kapphahn K, Cherin R. Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial. Obesity (Silver Spring). 2016 Jan;24(1):79-86. doi: 10.1002/oby.21331. Epub 2015 Dec 6.