© Vitamin Research Products Inc. 2001Fat, Obesity, Diabetes and Supplements
Part I
by Dr. Emmanuel Opara
Click Here to Read Part II
Type 2 diabetes constitutes more than 90% of all cases of diabetes mellitus. As many as 80% of individuals with type 2 diabetes are overweight or obese and obesity often precedes the development of diabetes. The development of obesity and insulin resistance depends on a complex interaction between genetic background and diet. Studies have shown that dietary fat is the primary nutritional stimulus for the development of obesity and the associated type 2 diabetes. Despite these findings, consumers are ambivalent towards fat in their foods. To help prevent the deleterious effects of fat consumption, people suffering from diabetes, those who are at risk such as persons with family history, and aged individuals who are deficient in antioxidants, would derive benefits by using appropriate doses of such supplements as vitamins C and E, L-glutamine, taurine, chromium and possibly ubiquinone and gymnema sylvestre. The mechanism of action and the effective doses of these supplements will be discussed in part II of this article.
Diabetes
As early as 1936, Himsworth observed that diabetes mellitus, which is characterized by high blood sugar levels, comprises two groups of patients; those who are insulin sensitive and others who are insulin resistant. It is now recognized that there are two major types of diabetes viz: type 1 diabetes or insulin -dependent diabetes mellitus (IDDM) and type 2 diabetes or non-insulin-dependent diabetes mellitus (NIDDM). The primary defect in type 1 diabetes resides in the pancreas, resulting in insulin deficiency and concomitant failure to metabolize glucose. In contrast, the problem in type 2 diabetes is predominantly attributable to the inability of the available insulin to work properly and this type of diabetes involves multiple organ systems, including abnormalities of insulin secretion, peripheral (muscle and adipose tissue) and hepatic insulin resistance. Most individuals with type 2 diabetes also suffer from excess body weight or obesity. Indeed, it has been reported that as many as 80% of NIDDM patients are overweight. Obesity often precedes type 2 diabetes and is now recognized as a major risk factor for the development of type 2 diabetes which constitutes more than 90% of all cases of diabetes mellitus1. This easily translates to a staggering number of persons with type 2 diabetes. In 1993, it was estimated that about 7.8 million Americans had diabetes, with type 2 comprising 95% of this number1. In addition to the diagnosed cases of type 2 diabetes, it is estimated that there is, at least, one undiagnosed case of type 2 diabetes for every diagnosed case, based on oral glucose tolerance testing in the second National Health and Nutrition Examination Survey (NHANES II).(1) Therefore, because of its preponderance and its relationship to obesity, type 2 diabetes will be the subject of this review.Diabetes mellitus is a chronic and potentially disabling disease which represents a major public health and clinical concern.(2) Individuals suffering from diabetes are at an increased risk of developing chronic complications related to ophthalmic, renal, neurological, cerebrovascular, cardiovascular, and peripheral vascular diseases. Consequently, people with diabetes are more likely than those without the disease to have heart attacks, strokes, amputations, kidney failure and blindness.(2) Furthermore, as a result of diabetes and its complications, persons with diabetes have more frequent and intensive encounters with the health-care system. In 1987, the economic costs of diabetes was estimated at $20.4 billion, of which 47% were direct medical expenditures. This estimate included some costs associated with chronic complications of diabetes but excluded the costs of surgical procedures, home health care, emergency rooms, ambulance services, services provided by licensed dietitians, physical therapy and costs associated with the late complications of diabetes. (2)
Prevention & Treatment
It is, therefore, imperative that healthy individuals should adopt effective strategies to prevent the development of diabetes and for individuals with the disease to seek beneficial ways to help treatment in order to avoid its devastations. As already pointed out, the overwhelming majority of cases of diabetes is NIDDM. Two major factors that play prominent roles in the development of type 2 diabetes are an individual's genetic predisposition and environmental influence such as lifestyle including dietary habits. In this two-part article, the role played by nutrients in the development of type 2 diabetes will be highlighted in the first part. In the second part, the focus will be on how the use of appropriate supplements can prevent the development of diabetes in individuals with family history of this disease and others at high risk, such as elderly people. Also, the use of supplements can positively affect the clinical course of the disease in those already suffering from type 2 diabetes and this will be discussed in part II .In a carefully designed study, the differential effects of fat and sucrose (carbohydrate) on the development of obesity and diabetes have been examined. (3) In the study, diabetes-prone C57BL/6J (B/6J) mice and diabetes-resistant A/J mice were fed one of four different diets, namely: a) high-fat, high-sucrose diet, b) high-fat, low-sucrose diet, c) low-fat, high-sucrose diet, d) low-fat, low-sucrose diet. After four months on these diets, it was found that B/6J mice gained more weight on both high-fat diets without consuming more calories than A/J mice. In the absence of fat, sucrose caused a decrease in body weight gain in both strains. Furthermore, whereas fat induced the development of insulin resistance characterized by hyperglycemia and hyperinsulinemia, sucrose had no effect on blood glucose and insulin levels.(3) These data clearly show that the development of obesity and insulin resistance depends on a complex interaction between genetic background and diet. In other studies performed in both humans and animal models, it has also been shown that fat is a primary nutritional stimulus for the development of obesity and the associated type 2 diabetes. Thus, the high content of fat in most Western diets accounts for the increased incidence of both obesity and diabetes in these populations. Any diet whose fat content equals or exceeds 30% of total calories should be considered high. However, consumers have an ambivalent attitude towards fat in their foods. The reason for this is, although high-fat consumption is associated with increased risk for obesity, diabetes and other diseases such as heart disease, fatty foods are known to make meals more palatable. The stability over years in fat intake suggests that consumers are unwilling to sacrifice the pleasure of eating fatty foods for health reasons.(4) A sensible compromise could be achieved under these circumstances if consumers are aware of nutritional supplements that would help to prevent the development of deleterious metabolic effects of dietary fat.
Oxidative stress & diabetic complications
Over three decades ago, Randle and colleagues proposed the "glucose-fatty acid cycle" hypothesis to explain the link between insulin resistance associated with type 2 diabetes and obesity. According to this hypothesis, excessive free fatty acid (FFA) release from adipose tissue for oxidation in muscle causes the production of metabolites that inhibit glucose utilization by the muscle. The metabolites identified at the time of Randle's report were all intermediates of the mitochondrial Krebs tricarboxylic acid cycle, such as ATP, citric acid and NADH. Recent studies have also shown that increased fatty acid availability from exogenous sources such as dietary fat, produces the same results as increased FFA mobilization from endogenous fat deposits. Furthermore, it is now being recognized that, in addition to the previous metabolites of fatty acid oxidation implicated in the glucose-fatty acid cycle, reactive oxygen species which are by -products of fatty acid oxidation also inhibit glucose metabolism resulting in sugar overload in the blood or hyperglycemia. It should be pointed out that during periods of increased fatty acid availability such as during high-fat feeding, there is increased peroxisomal fatty acid oxidation, mostly due to increased activity of the enzyme, catalase, a reaction that leads to excessive generation of hydrogen peroxide. Also, dietary fat may become rancid or undergo lipid peroxidation leading to the production of increased levels of lipid peroxides. These peroxides are reactive oxygen species which cause damage to cellular structures and impair glucose metabolism. Under normal circumstances, there is a delicate balance between reactive oxygen species (free radical) production and the levels of antioxidant defense mechanisms in the body. During periods of increased reactive oxygen species production, the antioxidant defense systems used by the body for detoxification, become overwhelmed. This results in the presence of toxic levels of reactive oxygen species which oxidize and inhibit the heme-containing glyceraldehyde-3-phosphate dehydrogenase enzyme of the glycolytic pathway and the cytochrome enzymes of the electron transport chain responsible for oxidative phosphorylation associated with Krebs cycle. The consequence of these inhibitory effects of reactive oxygen species on the enzymes involved in glucose oxidation is the development of hyperglycemia. Simultaneously, fatty acid oxidation by the pancreatic islets of Langerhans causes increased insulin output(5) that results in hyperinsulinemia. In this way, fat metabolism produces insulin resistance which precedes the development of clinical type 2 diabetes. In addition to the outlined role of reactive oxygen species in the pathogenesis of type 2 diabetes, the relationship between oxidative stress (increased free radical generation in the presence of reduced antioxidant availability) and diabetic complications has been extensively studied. In general, oxidative stress has been implicated in the development of both macro- and micro-vascular complications of diabetes.Dietary factors
The studies performed by Surwit and colleagues showed that although sucrose in the presence of low-fat caused an apparent decrease in body weight and had no effect on plasma insulin and glucose levels in the obesity- and diabetes-prone B /6J mice, the addition of this carbohydrate to a high-fat diet did exacerbate increases in body weight, plasma insulin and glucose levels induced by fat. This observation may be explained by the fact that some metabolites of fatty acid oxidation enhance endogenous glucose production by the liver in the face of reduced glucose utilization in the body caused by other metabolites and products of fatty acid oxidation. Also, high carbohydrate diets have been shown to stimulate lipogenesis and this phenomenon in the presence of abundant dietary fat would enhance fat storage and body weight gain. A zero percent fat diet is unrealistic and even if such a diet were to be formulated with very high content of carbohydrate, it would induce hyperlipidemia which over time may lead to metabolic abnormalities. The combined effect of fat and sucrose represents more closely the real life situation since most human diets comprise fat, carbohydrate and other nutrients in different proportions. This situation, therefore, demands the need for supplements that would take care of the unwanted side-effects of fat consumption.The study by Surwit and colleagues showed that diet did not affect plasma glucose and insulin levels in A/J mice but high-fat diets induced significant gains in body weight in this diabetes-resistant mouse strain. This observation may explain why some individuals gain significant body weight without developing diabetes. Type 2 diabetes is known to have a familial aggregation and studies of twins and offsprings of diabetic patients have provided a strong evidence for a role of the genetic component in the development of this disease.6 Although there is good evidence that type 2 diabetes may be determined by major genes in high -risk individuals, a polygenic mode of inheritance may not be responsible for glucose intolerance. In spite of increased search, no single specific marker for type 2 diabetes has yet been found but linkage in some families has been discovered.(6)
The incidence of diabetes increases with age. Impaired glucose tolerance (IGT) is clearly the first recognized stage in the development of type 2 diabetes and it has been reported that the prevalence of IGT reaches 23% at ages 65-74 years in the US population.(6) The are several reasons to explain the increased incidence of type 2 diabetes with age. First, aging appears to induce a specific defect in glucose-stimulated insulin secretion. This defect is an aspect of the global defect in glucose metabolism that generally occurs with aging and this has been attributed to multiple postbinding defects (including glucose transport) after insulin binding to its receptor. Second, abnormalities in insulin regulation of FFA /lipid metabolism secondary to increased fat mass and substrate competition between fat and glucose are present and appear to play a role in insulin resistance of human aging. Third, antioxidant defense systems are reduced with age. To prevent these changes that occur with aging, the need for supplements is apparent. Among the beneficial supplements for disease prevention are: antioxidants such as ubiquinone, vitamins C and E; supplements that enhance tissue antioxidant levels such as L-glutamine; other supplements that inhibit fatty acid oxidation such as L-glutamine and taurine, as well as those such as L-glutamine and chromium which promote blood glucose regulation through the reduction of body weight. In addition, the use of antioxidant supplements may also prevent the development of other age-associated diseases.
Summary
People suffering from diabetes, those who are at risk such as persons with family history, and aged individuals who are known to be deficient in antioxidant defense systems, would derive benefits by using appropriate doses of antioxidant supplements, such as vitamins C and E, and other supplements, such as L -glutamine and taurine which inhibit excessive fatty acid oxidation. Chromium supplement available as chromium picolinate has been found to be useful for weight loss and for blood sugar control. Lesser known supplements such as ubiquinone and gymnema sylvestre have also been reported to be efficacious in both prevention and treatment of diabetes. The mechanism of action and effective doses of these supplements will be discussed at great length in the second part of this article.Highly recommended source of nutrients and supplements.
Dr. Emmanuel C. Opara is a research professor in the Departments of Surgery and Cell Biology and is a member of the Sara W. Stedman Center for Nutritional Studies at Duke University Medical Center in Durham North Carolina.
