Cross-sectional assessment of pain and physical function in skeletal dysplasia patients.

Short stature skeletal dysplasia (SD) patients have orthopedic and neurologic complications causing significant pain and physical disability. We conducted a large cross-sectional online survey in 361 people with short stature SD (>10 years) to describe pain prevalence, characteristics, and the relationship between pain and function. Chronic pain prevalence per Brief Pain Inventory (BPI) was 70.3%. Women reported more pain than men (73% vs 63% p = 0.04). Pain Severity Score (average of current, worst, least and average pain) averaged 3.3 ± 2, while the Pain Interference Score (with daily activities) averaged 3.4 ± 2.7 on a 10-point scale. Per Bleck scale, 20.5% had little or no functional capacity. Increasing age and decreased ambulation independently predicted chronic pain. Chronic pain is prevalent in short stature SD patients and associated with poor physical function. Further study is required to clarify the temporal relationship among pain, function and treatments.

Effect of dietary macronutrient composition on tissue-specific lipoprotein lipase activity and insulin action in normal-weight subjects.

The effects of macronutrient composition on fasting and postprandial activities of adipose tissue lipoprotein lipase (ATLPL) and skeletal muscle LPL (SMLPL) and on insulin sensitivity (S(I)) were studied in 25 normal-weight subjects. Each subject was fed a high-carbohydrate (HC) diet for 16 d and a high-fat (HF) diet for 16 d, in randomized order. On day 15 of each diet, biopsies for ATLPL and SMLPL were done in the fasted state and 6 h postprandially. On day 16 of each diet, a euglycemic clamp was used to measure S(I). There was no effect of diet composition on fasting ATLPL or SMLPL. With both diets and in both tissues, LPL increased significantly from fasting to 6 h postprandially. In adipose tissue only there was a significant difference between the 2 diets in LPL meal response (HC >HF, P = 0.024). There was no effect of diet composition on S(I). After the HC diet only, there were significant correlations between fasting SMLPL and S(I), but not ATLPL. After the HF diet, associations between insulin action and LPL were evident only in the postprandial state. In summary, 16 d of HC compared with HF feeding in normal-weight subjects increased the responsiveness of ATLPL to an HC compared with an HF meal. However, the same diets had no effect on fasting ATLPL or SMLPL, the responsiveness of SMLPL to a meal, or S(I). These data suggest that in normal-weight subjects habitual dietary carbohydrate intake may have a stronger effect on subcutaneous fat storage than does dietary fat intake.

Isoproterenol and somatostatin decrease plasma leptin in humans: a novel mechanism regulating leptin secretion.

In cultured adipocytes, leptin is increased by insulin and decreased by cAMP. In animal models, insulin and agents that increase intracellular cAMP have been shown to similarly affect plasma leptin in vivo. This study was undertaken to test the hypothesis that in humans increased cAMP induced by isoproterenol would decrease leptin. Five groups of normal weight subjects were studied; 1) subjects infused with isoproterenol at a rate of 24 ng/kg/min (ISO24); 2) subjects infused with isoproterenol at a rate of 8 ng/kg/min (ISO8); 3) subjects infused with somatostatin/insulin/GH followed by coinfusion with 8 ng/kg/min isoproterenol (ISO8 + SRIH); 4) subjects infused with somatostatin/insulin/GH alone (SRIH); and 5) control subjects infused with saline (NS). ISO24 infusion resulted in a 27% decrease in plasma leptin over 120 min. ISO24 also increased plasma insulin over the infusion. ISO8 resulted in a 16% decrease in leptin. Saline did not change leptin. SRIH alone decreased leptin 19% over the first 120 min, however no additional fall was seen over the next 120 min the SRIH group. Nonetheless, the addition of 8 ng/kg/min ISO during the second 120 min (ISO8 + SRIH) caused a 15% further decline in plasma leptin. Therefore both isoproterenol and somatostatin reduce plasma leptin in humans. The effect of isoproterenol is likely mediated by beta-adrenergic receptors, whereas the effect of somatostatin suggests a novel mechanism for the regulation of leptin.

Tissue-specific regulation of lipoprotein lipase by isoproterenol in normal-weight humans.

Lipoprotein lipase (LPL) is a hydrolytic enzyme, involved in lipoprotein metabolism and nutrient partitioning, that is subject to tissue-specific regulation. Evidence for divergent regulation of the lipase by insulin has been demonstrated, but alterations in the tissue-specific response of LPL to catecholamines has not been studied in humans. The regulation of LPL in gluteal adipose tissue and vastus lateralis muscle by isoproterenol (epinephrine isopropyl homologue) in humans was examined over 2 h in subjects infused with 0 (saline) or 8 or 24 ng.kg-1.min-1 isoproterenol. The infusion of normal saline into control subjects failed to alter adipose tissue or skeletal muscle LPL activity. However, in the saline-infused subjects there was a positive correlation between the percent change in plasma norepinephrine concentrations and the percent change in muscle LPL activity (r = 0.826, P < 0.05). Isoproterenol infusion did not change LPL in either adipose tissue or muscle compared with saline-infused controls, but plasma insulin levels in addition to plasma glucose, free fatty acids, and glycerol were increased. To prevent the isoproterenol-induced hyperinsulinemia, a pancreatic clamp technique was utilized. An increase in muscle LPL was demonstrated (P = 0.037) with no change in adipose tissue LPL. The change in muscle LPL activity after the 2-h infusion correlated with the change in muscle mRNA (P = 0.021). Overall, these studies indicate that in humans the response of LPL to catecholamines is tissue specific with no effect in adipose tissue but a stimulation in skeletal muscle. Endogenous regulation of LPL in muscle by catecholamines could be important in muscle fuel metabolism and could relate to effects of adenosine 3',5'-cyclic monophosphate and/or fatty acids at the level of the LPL gene.

Periprandial systemic and regional lipase activity in normal humans.

An assay for plasma lipoprotein lipase activity was used without prior injection of heparin to study arteriovenous differences of lipases across skeletal muscle and adipose tissue of normal male volunteers. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and triglyceride?concentrations were measured in arterial plasma and in venous effluent plasma from forearm skeletal muscle and subcutaneous abdominal adipose tissue, in the postabsorptive state and after a mixed meal. Triglyceride clearance by the tissues was greater across adipose tissue than across muscle. There were no arteriovenous differences for HTGL activity. In the postabsorptive state skeletal muscle released LPL activity, but adipose tissue did not. Postprandially the arterial LPL and HTGL activities did not change. LPL activity in adipose tissue venous effluent rose, whereas that in muscle venous effluent decreased. These results show that the release of LPL from subcutaneous adipose and forearm tissues is regulated differently, reflecting in vivo differences in LPL regulation at the tissue level.

Weight regain following sustained weight reduction is predicted by relative insulin sensitivity.

Ten moderately obese women (body mass index 34.9 +/- 1.1 kg/m2, mean +/- SEM), had previously been through a 3-month weight loss program followed by 3 months of weight maintenance at the reduced weight. A euglycemic clamp for determination of insulin sensitivity was performed on each subject prior to weight loss, and another at the end of the weight maintenance phase. The mean weight loss for the group was 11.4 +/- 2.2 kg. The women were then seen for follow-up weights 12 months and 18 months after the conclusion of the weight maintenance period. All of the women except one had regained their weight by the time of the 12-month visit. It was found that the amount of weight regained both at 12 months and 18 months was correlated with the change in insulin sensitivity which occurred from the baseline study to after weight loss/maintenance. The data indicate that increased insulin sensitivity following sustained weight loss in obese women predicts weight regain.

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 (delta ATLPL) 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 delta ATLPL and glycohemoglobin (GHb) level (r = .883, P = .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Change in skeletal muscle lipoprotein lipase activity in response to insulin/glucose in non-insulin-dependent diabetes mellitus.

Skeletal muscle lipoprotein lipase (SMLPL) provides fatty acids to myocytes for lipoprotein triglyceride oxidation. In human obesity, an insulin-resistant state, SMLPL levels measured in the fasted state are either decreased or unchanged as compared with levels in normal-weight controls. However, insulin/glucose infusion increases SMLPL activity in obese individuals, whereas in normal-weight subjects the activity is decreased. One of the goals of this study was to determine the impact of obesity with concomitant non-insulin-dependent diabetes mellitus (NIDDM) on fasting SMLPL and on the change in SMLPL activity (delta MLPL) in response to an insulin/glucose infusion. Because NIDDM is often a more insulin-resistant state, it was hypothesized that SMLPL activity would be further increased by insulin/glucose in subjects who were obese and had NIDDM. Measurements of SMLPL were made from biopsies of vastus lateralis skeletal muscle taken before and after a 6-hour insulin/glucose infusion in the setting of a euglycemic clamp. Thirteen nondiabetic obese women (OBC) and six nondiabetic normal-weight women (NWC) were used as control subjects. SMLPL levels measured in the fasted state were significantly lower in obese NIDDM subjects as compared with either control group. Relative insulin action was determined by calculation of the mean glucose infusion rate (GIR) required to sustain euglycemia over the last 60 minutes of the infusion. For all three groups combined, representing a continuum of insulin sensitivity, there was a positive correlation between GIR and fasting SMLPL. As described earlier, in the NWC group SMLPL activity decreased significantly after 6 hours of insulin/glucose, and in the OBC group SMLPL increased after insulin/glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase.

Obesity is an increasingly prevalent problem, and long-term maintenance of the weight-reduced state is difficult for the obese individual. Following weight reduction, many metabolic changes occur. Among these is an increase in adipose tissue lipoprotein lipase (ATLPL), which predicts an alteration in lipid fuel partitioning which may then contribute to resumption of the obese state. The purpose of this study was to test whether changes in skeletal muscle LPL (SMLPL) and its response to insulin/glucose after sustained weight reduction also indicate a potential altered partitioning of lipid fuels away from oxidative pathways in muscle to storage in adipose tissue. Biopsies of vastus lateralis muscle were carried out in premenopausal obese women (n = 11, 94 +/- 4 kg, mean +/- SEM) before and after consumption of a 900 kcal day-1 diet for 3 months followed by 3 months of isocaloric maintenance of the reduced weight (n = 11, 82 +/- 4 kg). SMLPL activity was measured in the fasted state and after 6 h insulin/glucose infusion, before and after sustained weight loss. SMLPL activities were also measured in six normal weight women. Fasting SMLPL activity in obese women (3.9 +/- 0.3 nmol FFA min-1 g-1) was similar to that measured in normal weight control women (4.4 +/- 0.5). Unlike normal weight controls in whom a 6 h insulin/glucose infusion decreased SMLPL activity, in obese women the response of SMLPL was positive (normal weight vs. obese: delta -0.8 +/- 0.3 vs. delta 1.6 +/- 0.5, P = 0.002). Following maintained weight reduction, fasting SMLPL in the obese group was reduced to 1.2 +/- 0.3 (obese before weight loss vs. obese after: P = 0.0001). This change in fasting SMLPL activity following weight loss/maintenance correlated with the resultant change in percent body fat (r s = 0.663, P = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)

A preliminary investigation of ethical problems in publication and research.

This paper describes a preliminary study investigating the nature of publication and research ethics problems encountered by psychologists. Descriptions of 25 ethical dilemmas were written by 22 psychologists. Those dilemmas involved conflicts about authorship credit (13), plagiarism (9), unethical research (1), and other related problems (2). Stage of career did not determine the likelihood of their being confronted with an ethical dilemma. The most often cited causes of problems and sources of distress were unethical demands by more dominant individuals who were perceived to hold power over the respondents.

Dietary substitution of medium chain triglycerides in subjects with non-insulin-dependent diabetes mellitus in an ambulatory setting: impact on glycemic control and insulin-mediated glucose metabolism.

OBJECTIVE: We have previously shown in an acute inpatient setting that dietary substitution of 77.5% of fat kcal as medium chain triglycerides (MCT) increased insulin-mediated glucose metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM), and that this effect appeared to be mediated by increases in insulin-mediated glucose disposal. The purpose of this study was to test the application of dietary substitution of medium chain triglycerides as an adjunctive tool in ambulatory therapy of NIDDM. METHODS: Five subjects with NIDDM underwent a baseline 6 hour insulin/glucose euglycemic clamp study, with simultaneous 3H-glucose infusion for calculation of glucose disposal rate and hepatic glucose output. Subjects were then randomized to begin one of two 30-day experimental diets, with long chain (LCT) or medium chain triglycerides (MCT), and subsequent crossover to the other diet. A 6 hour euglycemic clamp was repeated after each diet phase. RESULTS: Diet records and urinary organic acid excretion indicated a high level of dietary compliance by the study participants. Postprandial blood glucose excursions were less after one month on the diet with MCT than after the LCT diet (p = 0.004). However, fasting serum glucose, serum fructosamine (a measure of glycemia), fasting insulin, hepatic glucose output, and insulin-mediated glucose metabolism were not improved by the dietary substitution of MCT. CONCLUSION: These data indicate that supplementation of a tolerable amount of MCT in a conventional diabetic exchange diet has little impact on glycemic control in subjects with NIDDM in an ambulatory setting.

Suction lipectomy: outcome relates to region-specific lipoprotein lipase activity and interval weight change.

To determine the effects of suction lipectomy on regional adipose tissue metabolism, nine women had repetitive circumferential measurements and biopsies of subcutaneous adipose tissue from a lipectomy site (site A) and a nonlipectomy site (site B) up to 12 months following lipectomy. Maximum reductions from preoperative baseline in weight, body mass index, and circumferences of sites A and B occurred at 3 months. Because of variable long-term compliance (6 to 12 months), we created a "last visit" time-point to assess adequately the effects of lipectomy for each individual. Not all subjects maintained reduction in site circumferences from 3 months to the last visit. The change in circumference of site A for that period was highly correlated with the change in circumference of site B (r = 0.828, p = 0.005). The change in circumference of site B, but not site A, at 3 months was related to the weight change above the weight of adipose tissue removed at suction lipectomy. Five subjects who were "sustained responders" to the lipectomy procedure were able to maintain or decrease circumferences of sites A and B from 3 months to the last visit. In contrast, four "limited responders" actually increased circumference of site A and had either no change or increased circumference of site B from 3 months to the last visit. The changes in circumference in both sites between 3 months and the last visit related to changes in body weight over the same interval. Ultimately, the decrement in circumference of site A was 3.4 percent (-2.4 cm) greater than that of site B (p = 0.0001). The response to lipectomy in site B, but not site A, between 3 months and the last visit was related to the change in fasting adipose tissue lipoprotein lipase from baseline to 3 months (r = 0.728, p = 0.026). This change in lipase activity in the control region may represent a metabolic defense of body weight in response to adipose tissue removal in the lipectomy site.

Methicillin-resistant Staphylococcus aureus in a nursing home and affiliated hospital: a four-year perspective.

OBJECTIVES: To determine the effect of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak in a nursing home on the subsequent MRSA caseload in a closely affiliated hospital. DESIGN: Observational and descriptive; routine and special MRSA surveillance data for nursing home and hospital were reviewed for a four-year period (1988 to 1991) as were records regarding patient transfers from nursing home to hospital. SETTING: The 120-bed nursing home care unit (NHCU) and the geographically separate 434-bed acute care facility (hospital) of the Portland Veterans' Affairs Medical Center (PVAMC). PATIENTS: Veterans hospitalized in the acute care division of NHCU. RESULTS: Following the introduction of MRSA into the NHCU in December 1987, it quickly disseminated. Two to 32 newly colonized or infected patients were recognized in each quarter of the study period. Facility-wide prevalence surveys on two occasions disclosed MRSA colonization rates of 34% and 10%. During the study period, 15 to 54 (mean: 37.6) patients were transferred each quarter from the NHCU to the hospital of the PVAMC. The number of MRSA cases transferred ranged from 0 to 16 per quarter (mean: 5.4). During the same period, the total number of MRSA cases in the hospital increased, rising from 7 cases in 1987 to 16 in 1988, 48 in 1989, 34 in 1990, and 35 in 1991. The percentage of hospital MRSA cases accounted for by NHCU transfers was 0% in 1988, 38% in 1989, 12% in 1990, and 11% in 1991. CONCLUSIONS: Despite the steady flow of patients between the NHCU and the hospital, the MRSA outbreak in the NHCU was associated with only a modest increase in the MRSA caseload at the affiliated hospital.

Tissue-specific lipoprotein lipase: relationships to body composition and body fat distribution in normal weight humans.

Twenty-six normal weight subjects (22 female, 4 male) were studied to determine the relationships of fasting levels of lipoprotein lipase in gluteal adipose tissue (ATLPL) and skeletal muscle (SMLPL) to body composition and body fat distribution. No relationship was found between fasting gluteal ATLPL and percent (%) body fat. There was, however, an inverse relationship between fasting SMLPL (from the vastus lateralis) and %body fat (p=0.005). A strong inverse correlation was also seen between fasting ATLPL and waist/hip ratio (p=0.0006), a measurement of body fat distribution. These relationships existed with or without the male subjects included. The tissue-specific relationships of lipoprotein lipase to body composition and body fat distribution could relate to the development of obesity or the maintenance of normal body weight by the effects of the lipase on the partitioning of lipoprotein triglyceride fatty acids.

Dietary substitution of medium-chain triglycerides improves insulin-mediated glucose metabolism in NIDDM subjects.

Dietary medium-chain triglycerides (MCT) may improve insulin-mediated glucose metabolism. To examine this possibility, 10 non-insulin-dependent diabetes mellitus (NIDDM) patients, 4 hypertriglyceridemic, and 6 normotriglyceridemic nondiabetic control subjects were examined with a 5-day cross-over design, in which the short-term metabolic effects of a 40% fat diet containing 77.5% of fat calories as MCT were compared with an isocaloric long-chain triglyceride-containing diet. In diabetic patients, MCT failed to alter fasting serum glucose concentrations but reduced preprandial glycemic excursions by 45% (F = 7.9, P less than 0.01). On MCT, the amount of glucose needed to maintain euglycemia during an intravenous insulin infusion was increased in diabetic subjects by 30%, in hypertriglyceridemic subjects by 30%, and in normotriglyceridemic control subjects by 17%. MCT increased mean +/- SE insulin-mediated glucose disposal (4.52 +/- 0.56 vs. 2.89 +/- 0.21 mg.kg-1.min-1; n = 3, P less than 0.05) but failed to alter basal glucose metabolism or insulin-mediated suppression of hepatic glucose output. Metabolic responses to MCT were observed independent of sulfonylurea therapy or severity of fasting hyperglycemia. No change in fasting serum insulin or triglyceride concentrations were seen with MCT administration. Although MCT increased mean fasting serum beta-hydroxybutyrate levels from 0.10 +/- 0.03 to 0.26 +/- 0.06 mM (P less than 0.05) in normotriglyceridemic nondiabetic subjects, no change was seen in diabetic patients. Thus, MCT-containing diets increased insulin-mediated glucose metabolism in both diabetic patients and nondiabetic subjects. In diabetic subjects, this effect appears to be mediated by increases in insulin-mediated glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

Preheparin lipoprotein lipolytic activities: relationship to plasma lipoproteins and postheparin lipolytic activities.

To determine the putative metabolic relevance of preheparin versus postheparin lipoprotein lipases, the relationships of both pre- and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) to plasma triglycerides, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol were determined in 93 men. Relationships of preheparin lipases to their respective postheparin lipases were also examined. Although relationships between the preheparin lipases and plasma triglycerides and HDL cholesterol were not apparent, both preheparin LPL (rs = 0.306, P = 0.0036) and HTGL (rs = 0.348, P = 0.0008) correlated with LDL cholesterol, a relationship not seen with either postheparin lipase. Both postheparin LPL (rs = 0.515, P = 0.0001) and postheparin HTGL (rs = -0.228, P = 0.0028), however, correlated with HDL cholesterol. In addition, postheparin LPL was inversely correlated with postheparin HTGL (rs = -0.363, P = 0.0003), whereas the relationship between preheparin LPL and preheparin HTGL was positive (rs = 0.228, P = 0.0009). Overall, these data point to differences between pre- and postheparin lipases in their relationships to lipoproteins, and one to another. The relationships of LDL cholesterol to both preheparin LPL and HTGL suggest that displacement of active forms of both lipases from their endothelial binding sites may mark triglyceride-rich lipoproteins or their remnants for metabolic pathways that lead to LDL.

Regional similarities in the metabolic regulation of adipose tissue lipoprotein lipase.

Seven normal weight and 10 obese women were studied to determine the relative activities of adipose tissue lipoprotein lipase (ATLPL) in the gluteal and abdominal subcutaneous adipose tissue depots, both in the fasting state and in response to a 6-hour insulin/glucose infusion. In normal weight women, fasting gluteal enzyme activity was greater than abdominal (P less than .02). In the obese group, fasting levels of ATLPL were higher in both the gluteal and abdominal depots than in the normal weight group, but similar between regions. The regulation of ATLPL by insulin/glucose was also similar between regions in each group. When both groups were considered together, there was a strong correlation between fasting ATLPL of both regions, and between the insulin responsiveness of gluteal ATLPL and abdominal ATLPL after a 6-hour infusion. Despite regional differences in fasting ATLPL in lean women, these studies indicate that the regulation of ATLPL by insulin/glucose is largely similar in at least these two subcutaneous adipose tissue depots.

Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in normal-weight humans.

Eight normal-weight subjects (four men, four women) were studied to determine the relative activities of lipoprotein lipase (LPL) in adipose tissue (ATLPL) and vastus lateralis skeletal muscle (SMLPL), both in the fasting state and in response to a 6-hour insulin/glucose infusion. Mean fasting levels of ATLPL and SMLPL were not statistically different. After 6 hours of insulin/glucose infusion, mean ATLPL activity was significantly greater than the fasting level (P less than .01), while mean SMLPL activity decreased from basal (P less than .05). These tissue-specific changes in LPL responsiveness (0 to 6 hours) were significantly different (P less than .01). No differences between men and women were observed. These divergent tissue-specific LPL responses to insulin/glucose would serve to direct lipoprotein triglyceride-derived fatty acids away from muscle and to adipose tissue for storage.

HDL subfractions and adipose tissue metabolism in the reduced-obese state.

The effect of weight reduction on fasting serum lipids and lipoproteins and adipose tissue lipoprotein lipase responsiveness to insulin was assessed immediately after and 3 mo subsequent to a mean 11.7% weight reduction in 14 women. Whereas reduction in fasting serum triglycerides persisted after 3 mo, reductions in serum cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein (HDL) cholesterol were not found at 3 mo. In fact, at 3 mo, levels of HDL cholesterol were higher than before weight reduction. Maintenance of the reduced-obese state also increased the HDL2-to-HDL3 cholesterol ratio (P less than 0.01), an effect strongly associated with the change in the responsiveness of adipose tissue lipoprotein lipase to insulin (r = 0.821, P less than 0.001). Moreover, after maintenance of the reduced-obese state, the HDL2-to-HDL3 cholesterol ratio also increased after the ingestion of corn oil and a 6-h insulin-glucose infusion, a response not present before weight reduction. Thus the effect of weight reduction on serum lipids and lipoproteins was not only time dependent, but for HDL, was strongly associated with changes in adipose tissue metabolism.