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 less than .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 less than .05) and VLDL
apoB (5.6 +/- .4 vs. 7.5 +/- 0.7, P less than .05) as compared with controls; fractional catabolic rates increased after
therapy (to 13.3 +/- 1.5, P less than .05, and 6.7 +/- .4, P less than .05, respectively). In the diabetics, this decrease in clearance was accompanied by a lower adipose
lipoprotein lipase (.30 +/- .09 vs. .92 +/- .25 mumol X g-1 X h-1, P less than .01), which increased during
therapy (to .61 +/- .17, P less than .05). Hepatic
lipase also decreased significantly after
therapy (27.4 +/- 3.6 to 26.4 +/- 3.2, P less than .01). Composition of VLDL in diabetics was also abnormal, indicated by a higher TG/
apoB ratio (14.7 +/- .6 vs. 11.7 +/- .8, P less than .01); this ratio fell during
therapy (to 12.5 +/- .8, P less than .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.