Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects

Abstract

Considerable controversy exists over the purported role of obesity in causing hyperglycemia, hyperlipemia, hyperinsulinemia, and insulin resistance; and the potential beneficial effects of weight reduction remain incompletely defined. Hypertriglyceridemia is one of the metabolic abnormalities proposed to accompany obesity, and in order to help explain the mechanisms leading to this abnormality the following sequential hypothesis is proposed: insulin resistance → hyperinsulinemia → accelerated hepatic triglyceride (TG) production → elevated plasma TG concentrations. To test this hypothesis and to gain insight into both the possible role of obesity in causing the above metabolic abnormalities and the potential benefit of weight reduction, the effects of weight loss on various aspects of carbohydrate and lipid metabolism were studied in a group of 36 normal and hyperlipoproteinemic subjects. Only weak to absent correlations (r = 0.03 - 0.46) were noted between obesity and the metabolic variables measured. This indicates that in the study group obesity cannot be the sole, or even the major, cause of these abnormalities in the first place. Further, marked decreases after weight reduction were observed in fasting plasma TG levels (mean value: pre weight reduction, 319 mg/100 ml; post weight reduction, 180 mg/100 ml) and cholesterol (mean values: pre weight reduction, 282 mg/100 ml; post weight reduction, 223 mg/100 ml) with a direct relation between the magnitude of the fall in plasma lipid values and the height of the initial plasma TG level. Significant decreases after weight reduction were also noted in the insulin and glucose responses during the oral glucose tolerance test (37% decrease and 12% decrease, respectively). Insulin and glucose responses to liquid food before and after weight reduction were also measured and the overall post weight reduction decrease in insulin response was 48% while the glucose response was relatively unchanged. In a subgroup of patients both the degree of cellular insulin resistance and the rate of hepatic very low density (VLDL) TG production before and after weight reduction were studied. These subjects demonstrated significant decreases after weight reduction in both degree of insulin resistance (33% decrease) and VLDL TG production rates (40% decrease). Thus, weight reduction lowered each of the antecedent variables (insulin resistance, hyperinsulinemia, and VLDL TG production) that, according to the given hypothesis, lead to hypertriglyceridemia, thus strengthening the overall scheme. Furthermore, the consistent decreases in plasma TG and cholesterol levels seen in all subjects lead to the conclusion that weight reduction is an important therapeutic modality for patients with endogenous hypertriglyceridemia.