Introduction
Human and many other animals, possess a metabolism that is geared towards storage of energy – as fat – at every possible opportunity. Unfortunately, in modern, affluent societies, where food is rarely lacking and physical exertion often unnecessary, this can lead to an excessive accumulation of fat and individuals become overweight or obese. The problem is particularly striking in some ethnic groups when they are introduced to a “Western “ life style with a diet containing convenience foods that are rich in fats and sugars and high in calories. Obesity causes a large number of distressing symptoms and is associated with increased morbidity and reduced life expectancy. The burden or excess weight puts strain on muscles and joints, causing arthritis and respiratory problem. Obesity disturbs normal homoeostatic mechanisms, precipitating the development of impaired glucose tolerance (IGT), Type 2 (non-insulin-dependent) diabetes and cardiovascular disease (CVD) in predisposed individuals.
Definitions and criteria
The most commonly used system for assessing fat is the Quetelet's Index.
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Body fat distribution
People with central obesity – that is with the 'android' pattern of obesity – are far more likely to develop Type 2 diabetes than those with lower body or ‘gynoid’ obesity.
Waist-hip ratio gives a reasonable indication of central obesity, and has been shown to be correlated with Type 2 diabetes in a number of studies. The ‘gold standard’ for detecting excessive visceral fat deposition is computed tomographic scanning. A study in Japanese American men, using this technique, showed that intro-abdominal fat deposition was more closely correlated with Type 2 diabetes than subcutaneous fat in the abdomen, in contrast, subcutaneous fat deposits in the abdomen, thorax or thigh were not statistically significant predictors.
Related Risk Factors
Fat intake
Since obesity is such an important predictor of Type 2 diabetes, it may be assumed that a caloric intake in excess of need is also a risk factor, if it leads to obesity. However, there is some evidence that the type of food consumed is also important. Dietary fat is the most likely dietary component to have some aetiological relationship with diabetes. Insulin resistance tends to develop in rats fed high-fat diets, and it is possible that a similar phenomenon may occur in humans, especially with a high intake of saturated fats. Cross – sectional data indicated that fats intake is higher in diabetic than in nondiabetic adults.
Lack of physical activity
After obesity, lack of physical activity is another important risk factor for the development of Type 2 diabetes. The British Regional Heart Study found that men who habitually engaged in moderate levels of physical activity had a substantially reduced risk of diabetes compared with physically inactive men, even after adjustment for age, BMI and other risk factors. Thus, although lack of exercise may act indirectly by contributing to the development of diabetes, it also appears to act independently. High levels of physical activity are correlated with lower level of plasma insulin, and physical training can decrease insulin resistance.
How does obesity cause diabetes ?
Central distribution of fat is associated with many pathogenetic factors that contribute to the disruption of normal glucose homeostasis (high plasma free fatty acids (FFAs), increased hepatic glucose production, peripheral insulin resistance). Generalised obesity may contribute to impaired glucose homeostasis through similar mechanisms, albeit to a much lesser degree.
Insulin resistance
Insulin resistance is probably fundamental to the link between obesity and diabetes. Nondiabetic members of populations with a high incidence of Type 2 diabetes, such as Hispanic Americans, Mexican Americans and Pima Indians all have higher basal plasma insulin levels than nondiabetic white Americans.
Hyperinsulinaemia and insulin resistance are also linked. Not just to BMI, but specifically to abdominal adiposity. A study using CT scanning showed that the amount of visceral adipose tissue had a significant positive correlation with hyperinsulinaemia and was negatively associated with insulin sensitivity.
Impaired glucose tolerance
Current recommendations define IGT as glucose levels during the oral glucose tolerance test that are intermediate between normal and diabetic values (2 hour value 140 – 200 mg %). IGT appears to represent a prediabetic state, although not all individuals with IGT go on to develop diabetes. In the US population, about one in ten adults have IGT and the incidence rises with age-nearly one in four adults aged 64 to 74 years are affected. Studies show a strong link between IGT & obesity.
Evolution from obesity to diabetes
Obese individuals with normal glucose tolerance are insulin resistant but are able to maintain normal glucose tolerance because their beta cells are able to compensate for insulin resistance. These compensatory mechanisms are hyperinsulinaemia and postprandial hyperglycaemia which prevent a defect in glucose uptake & especially Glucose storage. Finally, with time, insulin secretion gradually decreases as a consequence of chronic hyperglycaemia and results in full pancreatic decompensation. At this stage, hepatic glucose production is increased. The most important factor in the evolution from obesity to diabetes resides in the permanence of the increase in lipid oxidation and mainly in the duration of obesity.
The glucose – fatty acid cycle
One of the most important factors triggering and maintaining the progression from obesity to diabetes appears to be an increase in availability and oxidation of FFAs. This leads, via the glucose fatty acid cycle, to defects in the oxidative and non-oxidative pathways of glucose metabolism and impairment in glucose utilization.
Individuals with a preponderance of central fat are characterized by hepatic insulin resistance and increased FFA turnover and presumably, oxidation. Circulating FFAs by a substrate competition mechanism, can potentially increase liver glucose output and impair glucose removal by the peripheral tissues. This in turn may lead to insulin resistance.
The following pattern of phenomenon can be observed :
- Increased FFA disposal / oxidation is paralleled by an increased rate of lipid oxidation
- Increased FFA oxidation is concomitant with and paralleled by a decrease in glucose oxidation, and possibly in glucose storage and by an impairment in insulin – mediated inhibition of hepatic glucose production
- As the glucose tolerance deteriorates, more and more lipids are oxidized and less and less glucose is oxidized and stored
- There is a parallel deterioration of hepatic insulin sensitivity
Since lipoprotein lipase activity is decreased, a decreased clearance of triglycerides also occurs. A characteristic pattern of dyslipidaemia therefore emerges, linked to visceral obesity.
- Raised very low density lipoprotein (VLDL)
- Raised triglycerides
- Reduced high density lipoprotein cholesterol (HDL)
- Increased small dense low density lipoprotein cholesterol (LDL) particles.
Alterations in the metabolisms of gluco-corticoids and sex steroids may also be involved in the interaction between visceral obesity, dyslipidemia and diabetes. |
