Effects of NIDDM on Very-Low-Density Lipoprotein Triglyceride and Apolipoprotein B Metabolism: Studies Before and After Sulfonylurea Therapy

Abstract

To evaluate mechanisms of diabetes-induced changes in very-low-density lipoprotein (VLDL), VLDL triglyceride (TG) and VLDL apolipoprotein B (apoB) metabolism were studied in 12 obese Pima Indian control subjects and in 15 Pima Indian obese non-insulin-dependent diabetics. Eleven of the diabetics were restudied after reduction of hyperglycemia with oral sulfonylurea therapy. In addition, adipose, muscle, and postheparin lipoprotein lipase and postheparin hepatic lipase activities were measured in all subjects. Obese diabetics as compared with obese controls showed a trend toward increased production of VLDL TG (46 ± 4 vs. 35 ± 6 g/day, P = .10) but not of VLDL apoB (1595 ± 106 vs. 1597 ± 164 mg/day, NS); production of VLDL TG declined to control levels (33 ± 4 g/day, P < .05) during therapy, whereas there was no change in production of VLDL apoB. Diabetics had a clearance defect for VLDL, indicated by significantly lower fractional catabolic rates for both VLDL TG (10.6 ± .9 vs. 13.1 ± .9 pools/ day, P < .05) and VLDL apoB (5.6 ± .4 vs. 7.5 ± 0.7, P < .05) as compared with controls; fractional catabolic rates increased after therapy (to 13.3 ± 1.5, P < .05, and 6.7 ± .4, P < .05, respectively). In the diabetics, this decrease in clearance was accompanied by a lower adipose lipoprotein lipase (.30 ± .09 vs. .92 ± .25 μmol · g−1 · h−1 P < .01), which increased during therapy (to .61 ± .17, P < .05). Hepatic lipase also decreased significantly after therapy (27.4 ± 3.6 to 26.4 ± 3.2, P < .01). Composition of VLDL in diabetics was also abnormal, indicated by a higher TG/apoB ratio (14.7 ± .6 vs. 11.7 ± .8, P < .01); this ratio fell during therapy (to 12.5 ± .8, P < .05). The data indicate there are multiple abnormalities in structure and metabolism of VLDL in non-insulin-dependent diabetics. Control of hyperglycemia with sulfonylureas has the capability of reversing some of these abnormalities.