Isocaloric Dietary Interventions for Insulin Resistance and the Metabolic Syndrome
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Obesity
- Sponsor
- Rockefeller University
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Change in hepatic insulin sensitivity from the first testing battery (on Western diet) to the second testing battery (on study diet). Hepatic insulin sensitivity will be assessed using the homeostatic model assessment plasma
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
In recent decades, the prevalence of obesity has increased dramatically in the United States. Obesity has been associated with an increased risk of the metabolic syndrome, which is characterized by a cluster of metabolic derangements, including insulin resistance, high blood sugar, high triglycerides, low high density lipoprotein (HDL) cholesterol levels, high blood pressure, and inflammation. Lifestyle interventions, including dietary modification, physical activity, and weight loss, form the basis of treatment for individuals with the metabolic syndrome. However, the optimal composition of the diet is not known at this time. Furthermore, due to hormonal and metabolic changes that accompany weight loss, most people find it very difficult to maintain significant weight reductions over time. As a result, weight regain is exceedingly common.
Detailed Description
Several dietary patterns, including the Dietary Approaches to Stop Hypertension study diet (the DASH diet) and the low glycemic index diet (low GI diet), may be useful in the treatment of individuals with the metabolic syndrome, even if body weight stays the same. Novel findings from our own pilot study suggest that these dietary patterns may improve insulin resistance and some other features of the metabolic syndrome, even after just two weeks and in the absence of weight loss. In this important follow-up study, the metabolic effects of the DASH diet and the low GI diet will be compared to those of an Western-style control diet. At least 39 overweight, insulin-resistant volunteers with the metabolic syndrome will be studied during a 32-day inpatient admission. All food will be provided, and body weight will be kept stable throughout the study. Subjects will first undergo testing after consuming a Western-style diet for two weeks. They will then be randomized to one of three study diets: the DASH diet, the low GI diet, or the Western-style diet. Testing will again be conducted after 2 weeks of weight stability on the study diet. Testing will include the assessment of insulin sensitivity and other metabolic parameters, such as blood sugar and cholesterol levels, blood pressure, and inflammation. This study will provide important information about the effects of these promising dietary patterns on features of the metabolic syndrome, in the absence of weight loss.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Nonsmoking men and postmenopausal women, ages 18 -
- •Premenopausal women who would not be expected to have significant fluctuations in estrogen and progesterone levels during the study (e.g. those on continuous monophasic hormonal contraception) may be included in the study at the discretion of the PI or designated study staff.
- •Body mass index (BMI) of at least 27 kg/m2
- •Body weight \< 200 kg (the weight limit of the Bod Pod® scale)
- •Evidence of insulin resistance, as suggested by any one of the following:
- •Fasting glucose of 100 mg/dL or higher
- •Impaired glucose tolerance, with a glucose concentration of 140 mg/dL or higher, 2 hours after a 75-gram oral glucose challenge.
- •A fasting insulin concentration of 9 mIU/L or higher
- •Willingness to consume only study food and drink for the duration of the study
- •Willingness to be randomized to any one of the three study diets
Exclusion Criteria
- •Current tobacco smoking
- •History of a bleeding disorder
- •Known or suspected cardiovascular disease, including angina, myocardial infarction, medical or surgical treatment for atherosclerotic disease, arrhythmia, or congestive heart failure
- •Blood pressure higher than 145/90 after 10 minutes of rest, confirmed on two or more visits, or treatment with three or more antihypertensive agents at any blood pressure. Subjects taking up to two antihypertensive agents may be included in the study if 1) BP is at least 115/75 mmHg but \< 145/90 mmHg on these agents and 2) they agree to remain on the same medications (and same dosages) during the study, unless otherwise advised by a primary care provider or study investigators (e.g. the dosage may be reduced or the medication may be stopped if signs or symptoms of hypotension develop during the study)
- •Fasting glucose \> 165 mg/dL, glycosylated hemoglobin \> 8%, or any treatment with oral hypoglycemic agents, insulin sensitizing agents (e.g. metformin or thiazolidinediones), insulin, incretin mimetics (e.g. exenatide), amylin analogues (e.g. pramlintide), or endocannabinoid receptor antagonists (e.g. rimonabant). Volunteers with type 2 diabetes and a glycosylated hemoglobin level of 7.5% or higher will be encouraged to discuss treatment options (e.g. pharmacotherapy versus study participation) with their primary care providers before enrolling in the study
- •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. Daily, low-dose, inhaled or nasal glucocorticoids may be acceptable in some cases, at the discretion of the Principal Investigator.
- •Current treatment with over-the-counter or prescription weight loss medications, such as orlistat or sibutramine
- •History of bariatric surgery
- •Current treatment with any cholesterol-lowering medications, such as statins, niacin,fibrates, or ezetimibe
- •Hyperthyroidism or untreated hypothyroidism. Subjects with chronic, treated, stable hypothyroidism may be included in the study at the discretion of the Principal Investigator
Outcomes
Primary Outcomes
Change in hepatic insulin sensitivity from the first testing battery (on Western diet) to the second testing battery (on study diet). Hepatic insulin sensitivity will be assessed using the homeostatic model assessment plasma
Time Frame: 3 years
Secondary Outcomes
- Peripheral (muscle) insulin sensitivity, Glycemic control,Glycemic responses to a representative breakfast, Systemic inflammation, blood endotoxin levels, lipids, Systolic and diastolic blood pressure, body composition, and dietary satisfaction.(3 years)