Weight Loss Diet Study: Low Carb vs Low Fat

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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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)