Author: Kevin Barry Comerford
Publisher:
Published: 2012
Total Pages:
ISBN-13: 9781267758668
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Metabolic Syndrome (METS) is characterized by a clustering of risk factors associated with the development of cardiovascular disease and type 2 diabetes (T2D). These risk factors are often defined by enlarged waist circumference, hyperglycemia, hypertension, hypertriglyceridemia and low HDL-cholesterol, but the true hallmarks of METS are obesity and insulin resistance. Insulin resistance and obesity are causally linked to each other, and both of them also independently drive all of the other risk factors for METS. Polycystic ovary syndrome (PCOS) only affects women, but shares many common traits with METS. The purpose of this dissertation is to uncover some of the relationships between METS, PCOS, insulin resistance, body composition and diet in order to better understand, treat and prevent these complex epidemics. Endocrine dysfunction or hormonal imbalances are often both the cause and result of metabolic disorders. Many of these hormones are designed, biologically speaking, to deal with incoming energy from the diet as well as energy stored in the body. Hormones such as insulin, leptin and cortisol serve multiple metabolic purposes and act as energy mobilizers as well as to modulate energy storage and energy sensing tasks. However, hormones do not act alone; they act in concert and often influence the actions and levels of other hormones. Systemic hormones such as insulin, thyroid hormone and cortisol are major regulators of metabolism as well as regulators of many other endocrine functions, but there are also other classes of hormones that regulate metabolism, namely those specifically derived from adipose tissue that play intricate roles in most metabolic processes. Adipokines, or proteins released from adipose tissue, also play a critical role in inflammation, insulin resistance, energy storage and nutrient transport. The well-known adipokines of this nature are interleukins, TNF-alpha and adiponectin, but they are only part of the story. Fatty acid binding protein 4 (FABP4) or retinol binding protein 4 (RBP4) are two lesser known adipokines that have also shown strong correlations with obesity, insulin resistance and METS. Genetic deletions and overexpression of either of these molecules in animal models have dramatic effects on metabolism and alter how nutrients are transported, stored and utilized. In order to further investigate these relationships, obese subjects with METS were studied during two months of active weight loss to determine changes in adipokines, and insulin resistance parameters during two months of active weight loss. Blood was taken before and after weight loss and assayed for numerous biochemical markers including hormones, glucose, lipids and adipokines. Dual energy X-ray absorptiometry (DXA) and indirect calorimetry were used to determine the effects of weight loss on body composition and whole body energy metabolism, respectively. It was found that active weight loss among female participants resulted in significantly increased FABP4 levels which is contrary to the previous research that shows the levels decreasing after weight loss. It appears that the changes in circulating levels of FABP4 are very time dependent and vary depending on where a person is on a weight loss plan with active weight loss increasing the levels in response to adipose tissue flux and then decreasing levels later on in the weight maintenance stages. Serum RBP4 displayed a different pattern and did not change after weight loss in our study which agrees with some, but not all of the previous research. It is possible that changes in serum RBP4 require larger amounts of weight loss than was seen in our study. Another key factor to metabolism is body composition. The tissues that our bodies are primarily composed of such as muscle and fat, are responsible for the large majority of our metabolic processes. Muscle and fat constantly and continually crosstalk with one another. If either of these tissues are metabolically compromised due to dietary and/or hormonal reasons then the other tissue needs to compensate and will also likely become compromised if the system stressors are not addressed. Thus, the study of body composition which includes both quantity and quality of fat and muscle is a key component to understanding and treating metabolic disorders. This research interest has been addressed using a population of women with polycystic ovary syndrome (PCOS). This disorder is considered a gender specific presentation of METS (a.k.a. Syndrome X) and has even been labeled Syndrome XX. The objective of the study was to investigate the effects of increased lean mass on PCOS and parameters of insulin resistance using oral glucose tolerance test (OGTT), frequently sampled intravenous glucose tolerance test (FSIVGTT) and DXA technology. The findings showed strong correlations with insulin resistance and lean mass in this population. Although these novel findings were quite controversial as lean mass is primarily linked with insulin sensitivity, these findings were very recently confirmed by independent researchers in an article that was published in Experimental and Clinical Endocrinology & Diabetes after our original publication. There definitely appears to be a unique relationship with PCOS, hormones, muscle mass and insulin resistance that suggests that muscle quality is altered in this syndrome and is a determining factor in the insulin resistance associated with it. Most people are not born obese or insulin resistant. These conditions usually develop slowly over time and may manifest in METS if proper care is not taken. The condition of being `overweight' could be considered a transition state along a path moving towards obesity. It is in the `overweight, yet still healthy' state in which people can be easily identified by health care providers and targeted for prevention of further progression into obesity and its associated health risks. In order to determine the effects of modest dietary intervention capabilities, overweight yet healthy subjects were recruited to take a soluble fiber supplement derived from corn, twice daily with their meals. Weight and body composition via bioelectrical impedance analysis (BIA) as well as blood lipids, glucose, hormones and adipokines were measured to determine the effects of the supplement without altering the subjects' diets. It was found that a simple supplement could have fairly impressive effects on weight loss, lipid reduction and decreasing fasting insulin levels in overweight adults, potentially stymieing their transition into an obese, insulin resistant or METS state. Obesity, insulin resistance, PCOS and METS are all issues linked to endocrine dysfunction, alteration in body composition, diet and lifestyle. Certain simple and inexpensive nutritional interventions can aid weight loss and improve insulin sensitivity without the costs and side effects associated with prescription medications. One simple dietary modification is to add fiber to the diet, with an emphasis on soluble fiber. Increased dietary fiber has been shown to help with appetite control, reduced caloric absorption and has also proved to beneficially affect all risk factors for METS.
