Glycohemoglobin levels relate to the response of adipose tissue lipoprotein lipase to insulin/glucose in obese non-insulin-dependent diabetes mellitus

Adipose tissue lipoprotein lipase (ATLPL) is responsible for the provision of lipoprotein-derived fatty acids to adipocytes for storage as triglycerides. Fasting ATLPL has been shown to be decreased in non—insulin-dependent diabetes mellitus (NIDDM), an insulin-resistant state. Medically uncomplicated obesity, another state of relative insulin resistance, is associated with decreased stimulation of the enzyme in response to metabolic stimuli. It was therefore hypothesized that the increased insulin resistance of NIDDM would result in an even greater defect in the response of ATLPL to insulin/glucose. Gluteal adipose tissue biopsies were performed in 13 premenopausal obese women with NIDDM, before and after 6 hours of intravenous insulin and glucose. Metabolic data from these studies were then compared with those obtained from 26 nondiabetic obese women of similar age, weight, and fasting insulin concentration (obese controls [OBC]). As expected, fasting gluteal ATLPL activity was lower in the NIDDM group than in OBC (3.7 ± 0.9 v 11.1 ± 1.6 nmol free fatty acids [FFA]/min/10 6 cells, P = .0003). The change in ATLPL activity (ΔATLPL) in response to a 6-hour insulin/glucose infusion was not statistically different between the two groups (2.2 ± 1.1 v 4.7 ± 1.2, P = .114). However, in NIDDM subjects there was a strong positive relationship between ΔATLPL and glycohemoglobin (GHb) level ( r = .883, P = .0001). Moreover, when obese NIDDM subjects were divided into those with GHb values in the lower half of the range (median, 10.5%) versus those with values in the upper half, the effect of glycemic control on ΔATLPL was highly significant (ΔATLPL, −0.6 ± 0.9 nmol FFA/min/10 6 cells v 4.6 ± 1.4, P = .009). Because FFA were suppressed less by insulin/glucose in obese NIDDM subjects, it may be that the increase in ATLPL in response to insulin/glucose seen in those subjects under poorer glycemic control serves to counteract NIDDM-related defects in insulin-mediated antilipolysis, and thereby serves to maintain adipocyte volume and overall adipose tissue mass.