Isley, William L.

Little is known about the fate of the lipolytic products produced by the action of lipoprotein lipase (LPL) on circulating triglyceride-rich lipoproteins in humans. We studied eight lean, healthy male subjects after an overnight fast. Subjects received infusions of lipid emulsions containing triolein labeled with 3H on both the glycerol backbone and the fatty acid portion of the molecule; 14C glycerol and 14C oleate were coinfused to quantify the systemic and forearm release of 3H glycerol and 3H oleate resulting from LPL action. There was significant forearm uptake of both whole plasma triglyceride (presumed to represent primarily VLDL; extraction fraction 2.6 ± 0.6%, P < 0.005 vs. zero) and radiolabeled triglyceride derived from the lipid emulsion (a surrogate for chylomicrons; extraction fraction 31 ± 4%, P < 0.005 vs zero). Systemic clearance and forearm fractional extraction of glycerol was greater than that of oleate (P < 0.001 and P < 0.02, respectively). The systemic and forearm fractional release of LPL-generated glycerol were similar at 51 ± 4 and 59 ± 1%, respectively (NS). In contrast, the forearm fractional release of LPL-generated oleate was less than systemic fractional release (14 ± 2 vs. 36 ± 4%, P < 0.0001). These results indicate that there is escape, or spillover, of the lipolytic products of LPL action on triglyceride-rich lipoproteins in humans. They further suggest that LPL-mediated fatty acid uptake is an inefficient process, but may be more efficient in muscle than in adipose tissue.

OBJECTIVE—Multiple daily insulin injection programs are commonly accompanied by considerable glycemic variation and hypoglycemia. We conducted a randomized crossover design clinical trial to compare glargine with ultralente insulin as a basal insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS—To determine whether the use of glargine insulin as a basal insulin would result in a comparable HbA1c and less glycemic variation and hypoglycemia than ultralente insulin, 22 individuals (aged 44 ± 14 years [±SD], 55% men) with type 1 diabetes who were experienced with multiple daily insulin injections and had an HbA1c of <7.8% were randomized in a crossover design to receive either glargine or ultralente as the basal insulin for 4 months. Aspart insulin was used as the prandial insulin. Physicians providing insulin dose adjustment advice were masked to the type of basal insulin. RESULTS—Treatment with glargine resulted in lower mean HbA1c (6.82 ± 0.13 vs. 7.02 ± 0.13, difference: 0.2 ± 0.08, P = 0.026), less nocturnal variability (plasma glucose 49.06 ± 4.74 vs. 62.36 ± 5.21 mg/dl, P = 0.04), and less hypoglycemia (24.5 ± 2.99 vs. 31.3 ± 4.04 events, P = 0.05), primarily due to less daytime hypoglycemia (P = 0.002). On the other hand, serious hypoglycemia and average glucose concentration measured with continuous subcutaneous glucose monitoring did not differ. CONCLUSIONS—We conclude that while use of either ultralente or glargine as a basal insulin can result in excellent glycemic control, treatment with glargine is associated with slightly but significantly lower HbA1c and less nocturnal glycemic variability and hypoglycemia.